TY  - CONF
AU  - Stevanović, Danijela
AU  - Paunović, Verica
AU  - Vučićević, Ljubica
AU  - Misirkić Marjanović, Maja
AU  - Perović, Vladimir
AU  - Ristić, Biljana
AU  - Bošnjak, Mihajlo
AU  - Mandić, Miloš
AU  - Harhaji-Trajković, Ljubica
AU  - Janjetović, Kristina
AU  - Kosić, Milica
AU  - Lalošević, Jovan
AU  - Nikolić, Miloš
AU  - Bonači-Nikolić, Branka
AU  - Trajković, Vladimir
PY  - 2023
UR  - https://indico.bio.bg.ac.rs/event/4/attachments/6/492/Abstract%20Book-CoMBoS2-TMB.pdf
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6286
AB  - Introduction: Since the interaction between autophagy and virus-induced inflammation is complex,
we investigated the interplay between autophagy and inflammation in COVID-19 patients and THP-1
cells expressing SARS-Cov2 proteins NSP5 and ORF3a.
Methods: Autophagy markers in blood from 19 control subjects and 26 COVID-19 patients at hospital
admission and one week later were measured by ELISA, while cytokine levels were examined by flow cytometric bead immunoassay. The level of p62 in cells and its concentration in cell culture supernatants
was measured by immunoblot/ELISA. The mRNA levels of proinflammatory cytokines were measured
by RT-qPCR.
Results: IFN-α, TNF, IL-6, IL-8, IL-17, IL-33, and IFN-γ were elevated in COVID-19 patients at both time
points, whereasIL-10 and IL-1β were elevated at admission and one week later, respectively. Autophagy
markers LC3 and ATG5 were unchanged in COVID-19. The concentration of autophagic cargo receptor
p62 was significantly lower and positively correlated with TNF, IL-10, IL-17, and IL-33 at hospital admission, returning to normal levels after one week. The expression of SARS-CoV-2 proteins NSP5 or ORF3a
in THP-1 cells caused an autophagy-independent decrease/autophagy-inhibition-dependent increase
of intracellular and secreted p62. This was associated with an NSP5-mediated decrease inTNF/IL-10 mRNA
and an ORF3a-mediated increase inTNF/IL-1β/IL-6/IL-10/IL-33 mRNA levels. A genetic knockdown of p62
mimicked the immunosuppressive effect of NSP5, while a p62 increase in autophagy-deficient cells mirrored the immunostimulatory action of ORF3a.
Conclusion: The autophagy receptor p62 is reduced in acute COVID-19, and the balance between autophagy-independent decrease and autophagy blockade-dependent increase of p62 levels could affect
SARS-CoV-induced inflammation.
PB  - Belgrade: Institute of Molecular Genetics and Genetic Engineering, University of Belgrade
C3  - Abstract Book: CoMBoS2 - the Second Congress of Molecular Biologists of Serbia; 2023 Oct 6-8; Belgrade, Serbia
T1  - Autophagy receptor P62 regulates SARS-CoV-2-induced inflammation in COVID-19
SP  - 76
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_6286
ER  - 

@conference{
author = "Stevanović, Danijela and Paunović, Verica and Vučićević, Ljubica and Misirkić Marjanović, Maja and Perović, Vladimir and Ristić, Biljana and Bošnjak, Mihajlo and Mandić, Miloš and Harhaji-Trajković, Ljubica and Janjetović, Kristina and Kosić, Milica and Lalošević, Jovan and Nikolić, Miloš and Bonači-Nikolić, Branka and Trajković, Vladimir",
year = "2023",
abstract = "Introduction: Since the interaction between autophagy and virus-induced inflammation is complex,
we investigated the interplay between autophagy and inflammation in COVID-19 patients and THP-1
cells expressing SARS-Cov2 proteins NSP5 and ORF3a.
Methods: Autophagy markers in blood from 19 control subjects and 26 COVID-19 patients at hospital
admission and one week later were measured by ELISA, while cytokine levels were examined by flow cytometric bead immunoassay. The level of p62 in cells and its concentration in cell culture supernatants
was measured by immunoblot/ELISA. The mRNA levels of proinflammatory cytokines were measured
by RT-qPCR.
Results: IFN-α, TNF, IL-6, IL-8, IL-17, IL-33, and IFN-γ were elevated in COVID-19 patients at both time
points, whereasIL-10 and IL-1β were elevated at admission and one week later, respectively. Autophagy
markers LC3 and ATG5 were unchanged in COVID-19. The concentration of autophagic cargo receptor
p62 was significantly lower and positively correlated with TNF, IL-10, IL-17, and IL-33 at hospital admission, returning to normal levels after one week. The expression of SARS-CoV-2 proteins NSP5 or ORF3a
in THP-1 cells caused an autophagy-independent decrease/autophagy-inhibition-dependent increase
of intracellular and secreted p62. This was associated with an NSP5-mediated decrease inTNF/IL-10 mRNA
and an ORF3a-mediated increase inTNF/IL-1β/IL-6/IL-10/IL-33 mRNA levels. A genetic knockdown of p62
mimicked the immunosuppressive effect of NSP5, while a p62 increase in autophagy-deficient cells mirrored the immunostimulatory action of ORF3a.
Conclusion: The autophagy receptor p62 is reduced in acute COVID-19, and the balance between autophagy-independent decrease and autophagy blockade-dependent increase of p62 levels could affect
SARS-CoV-induced inflammation.",
publisher = "Belgrade: Institute of Molecular Genetics and Genetic Engineering, University of Belgrade",
journal = "Abstract Book: CoMBoS2 - the Second Congress of Molecular Biologists of Serbia; 2023 Oct 6-8; Belgrade, Serbia",
title = "Autophagy receptor P62 regulates SARS-CoV-2-induced inflammation in COVID-19",
pages = "76",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_6286"
}

Stevanović, D., Paunović, V., Vučićević, L., Misirkić Marjanović, M., Perović, V., Ristić, B., Bošnjak, M., Mandić, M., Harhaji-Trajković, L., Janjetović, K., Kosić, M., Lalošević, J., Nikolić, M., Bonači-Nikolić, B.,& Trajković, V.. (2023). Autophagy receptor P62 regulates SARS-CoV-2-induced inflammation in COVID-19. in Abstract Book: CoMBoS2 - the Second Congress of Molecular Biologists of Serbia; 2023 Oct 6-8; Belgrade, Serbia
Belgrade: Institute of Molecular Genetics and Genetic Engineering, University of Belgrade., 76.
https://hdl.handle.net/21.15107/rcub_ibiss_6286

Stevanović D, Paunović V, Vučićević L, Misirkić Marjanović M, Perović V, Ristić B, Bošnjak M, Mandić M, Harhaji-Trajković L, Janjetović K, Kosić M, Lalošević J, Nikolić M, Bonači-Nikolić B, Trajković V. Autophagy receptor P62 regulates SARS-CoV-2-induced inflammation in COVID-19. in Abstract Book: CoMBoS2 - the Second Congress of Molecular Biologists of Serbia; 2023 Oct 6-8; Belgrade, Serbia. 2023;:76.
https://hdl.handle.net/21.15107/rcub_ibiss_6286 .

Stevanović, Danijela, Paunović, Verica, Vučićević, Ljubica, Misirkić Marjanović, Maja, Perović, Vladimir, Ristić, Biljana, Bošnjak, Mihajlo, Mandić, Miloš, Harhaji-Trajković, Ljubica, Janjetović, Kristina, Kosić, Milica, Lalošević, Jovan, Nikolić, Miloš, Bonači-Nikolić, Branka, Trajković, Vladimir, "Autophagy receptor P62 regulates SARS-CoV-2-induced inflammation in COVID-19" in Abstract Book: CoMBoS2 - the Second Congress of Molecular Biologists of Serbia; 2023 Oct 6-8; Belgrade, Serbia (2023):76,
https://hdl.handle.net/21.15107/rcub_ibiss_6286 .

TY  - CONF
AU  - Mandić, Miloš
AU  - Misirkić Marjanović, Maja
AU  - Vučićević, Ljubica
AU  - Bošnjak, Mihajlo
AU  - Perović, Vladimir
AU  - Janjetović, Kristina
AU  - Paunović, Verica
AU  - Stevanović, Danijela
AU  - Kosić, Milica
AU  - Harhaji-Trajković, Ljubica
AU  - Trajković, Vladimir
PY  - 2023
UR  - https://www.sdir.ac.rs/en/
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6301
AB  - Background: Reactive oxygen species (ROS) have been implicated in autophagy induction and mitogen activated protein kinases (MAPK) activation which both participate in the differentiation of hematopoietic and leukemic cells. 
We assessed the role of ROS in MAPK activation and autophagy induction in phorbol myristate acetate-(PMA) induced macrophage differentiation of HL-60 leukemia cells. Material and methods: The macrophage markers CD11b, EGR1, 
CSF1R, and IL-8 were assessed by RT-qPCR and flow cytometry. The activation of MAPK was assessed by ERK and JNK immunoblotting, while autophagy was monitored by LC3-II and p62 immunoblotting. Pharmacological inhibition 
was used to determine the role of MAPK and autophagy in HL60 cell differentiation. Intracellular ROS production was determined by flow cytometric analysis of the green fluorescence emitted by non-selective redox-sensitive dye 2',7'-dichlorodihydrofluorescein diacetate. Antioxidant N-acetylcysteine (NAC) was used to determine the role of ROS in MAPK activation, induction of autophagy and HL-60 macrophage differentiation. Results: PMA-triggered differentiation of HL-60 cells into macrophage-like cells was confirmed by elevated expression of macrophage markers 
CD11b, EGR1, CSF1R, and IL-8. The induction of autophagy was demonstrated by the increase of autophagic flux. Pharmacological inhibition of ERK or JNK suppressed PMA-triggered autophagy induction and differentiation of HL-60 cells into macrophage-like cells. PMA increased the intracellular ROS generation and the antioxidant NAC reduced the expression of macrophage markers EGR-1, CSF1R, IL-8 and CD11b in PMA-treated HL-60 cells. NAC also blocked PMA-induced LC3-II and ERK phosphorylation, but only slightly reduced the phosphorylation of JNK and did not affect 
the levels of p62. Conclusion: Our study revealed the partial involvement of ROS in MAPK-dependent autophagy in the differentiation of HL60 cells, indicating ROS/MAPK-mediated autophagy for further investigation in differentiation therapy of AML.
PB  - Belgrade: Serbian Association for Cancer Research
C3  - Proceedings book of The Sixth Congress of The Serbian Association for Cancer Research with international participation: From Collaboration to Innovation in Cancer Research; 2023 Oct 2-4; Belgrade, Serbia
T1  - The role of ROS in MAPK-dependent autophagy involved in phorbol myristate acetate-induced macrophage differentiation of HL-60 leukemia cells
SP  - 104
EP  - 105
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_6301
ER  - 

@conference{
author = "Mandić, Miloš and Misirkić Marjanović, Maja and Vučićević, Ljubica and Bošnjak, Mihajlo and Perović, Vladimir and Janjetović, Kristina and Paunović, Verica and Stevanović, Danijela and Kosić, Milica and Harhaji-Trajković, Ljubica and Trajković, Vladimir",
year = "2023",
abstract = "Background: Reactive oxygen species (ROS) have been implicated in autophagy induction and mitogen activated protein kinases (MAPK) activation which both participate in the differentiation of hematopoietic and leukemic cells. 
We assessed the role of ROS in MAPK activation and autophagy induction in phorbol myristate acetate-(PMA) induced macrophage differentiation of HL-60 leukemia cells. Material and methods: The macrophage markers CD11b, EGR1, 
CSF1R, and IL-8 were assessed by RT-qPCR and flow cytometry. The activation of MAPK was assessed by ERK and JNK immunoblotting, while autophagy was monitored by LC3-II and p62 immunoblotting. Pharmacological inhibition 
was used to determine the role of MAPK and autophagy in HL60 cell differentiation. Intracellular ROS production was determined by flow cytometric analysis of the green fluorescence emitted by non-selective redox-sensitive dye 2',7'-dichlorodihydrofluorescein diacetate. Antioxidant N-acetylcysteine (NAC) was used to determine the role of ROS in MAPK activation, induction of autophagy and HL-60 macrophage differentiation. Results: PMA-triggered differentiation of HL-60 cells into macrophage-like cells was confirmed by elevated expression of macrophage markers 
CD11b, EGR1, CSF1R, and IL-8. The induction of autophagy was demonstrated by the increase of autophagic flux. Pharmacological inhibition of ERK or JNK suppressed PMA-triggered autophagy induction and differentiation of HL-60 cells into macrophage-like cells. PMA increased the intracellular ROS generation and the antioxidant NAC reduced the expression of macrophage markers EGR-1, CSF1R, IL-8 and CD11b in PMA-treated HL-60 cells. NAC also blocked PMA-induced LC3-II and ERK phosphorylation, but only slightly reduced the phosphorylation of JNK and did not affect 
the levels of p62. Conclusion: Our study revealed the partial involvement of ROS in MAPK-dependent autophagy in the differentiation of HL60 cells, indicating ROS/MAPK-mediated autophagy for further investigation in differentiation therapy of AML.",
publisher = "Belgrade: Serbian Association for Cancer Research",
journal = "Proceedings book of The Sixth Congress of The Serbian Association for Cancer Research with international participation: From Collaboration to Innovation in Cancer Research; 2023 Oct 2-4; Belgrade, Serbia",
title = "The role of ROS in MAPK-dependent autophagy involved in phorbol myristate acetate-induced macrophage differentiation of HL-60 leukemia cells",
pages = "104-105",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_6301"
}

Mandić, M., Misirkić Marjanović, M., Vučićević, L., Bošnjak, M., Perović, V., Janjetović, K., Paunović, V., Stevanović, D., Kosić, M., Harhaji-Trajković, L.,& Trajković, V.. (2023). The role of ROS in MAPK-dependent autophagy involved in phorbol myristate acetate-induced macrophage differentiation of HL-60 leukemia cells. in Proceedings book of The Sixth Congress of The Serbian Association for Cancer Research with international participation: From Collaboration to Innovation in Cancer Research; 2023 Oct 2-4; Belgrade, Serbia
Belgrade: Serbian Association for Cancer Research., 104-105.
https://hdl.handle.net/21.15107/rcub_ibiss_6301

Mandić M, Misirkić Marjanović M, Vučićević L, Bošnjak M, Perović V, Janjetović K, Paunović V, Stevanović D, Kosić M, Harhaji-Trajković L, Trajković V. The role of ROS in MAPK-dependent autophagy involved in phorbol myristate acetate-induced macrophage differentiation of HL-60 leukemia cells. in Proceedings book of The Sixth Congress of The Serbian Association for Cancer Research with international participation: From Collaboration to Innovation in Cancer Research; 2023 Oct 2-4; Belgrade, Serbia. 2023;:104-105.
https://hdl.handle.net/21.15107/rcub_ibiss_6301 .

Mandić, Miloš, Misirkić Marjanović, Maja, Vučićević, Ljubica, Bošnjak, Mihajlo, Perović, Vladimir, Janjetović, Kristina, Paunović, Verica, Stevanović, Danijela, Kosić, Milica, Harhaji-Trajković, Ljubica, Trajković, Vladimir, "The role of ROS in MAPK-dependent autophagy involved in phorbol myristate acetate-induced macrophage differentiation of HL-60 leukemia cells" in Proceedings book of The Sixth Congress of The Serbian Association for Cancer Research with international participation: From Collaboration to Innovation in Cancer Research; 2023 Oct 2-4; Belgrade, Serbia (2023):104-105,
https://hdl.handle.net/21.15107/rcub_ibiss_6301 .

TY  - CONF
AU  - Mandić, Miloš
AU  - Misirkić Marjanović, Maja
AU  - Vučićević, Ljubica
AU  - Bošnjak, Mihajlo
AU  - Perović, Vladimir
AU  - Ristić, Biljana
AU  - Ćirić, Darko
AU  - Janjetović, Kristina
AU  - Paunović, Verica
AU  - Stevanović, Danijela
AU  - Kosić, Milica
AU  - Harhaji-Trajković, Ljubica
AU  - Trajković, Vladimir
PY  - 2023
UR  - https://indico.bio.bg.ac.rs/event/4/attachments/6/492/Abstract%20Book-CoMBoS2-TMB.pdf
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6285
AB  - Introduction: Autophagy has been shown to participate in the differentiation of hematopoietic and
leukemic cells. We investigated the mechanisms of autophagy action in the differentiation induced by
PKC activator phorbol myristate acetate (PMA) in HL-60 acute myeloid leukemia cells.
Methods: The macrophage markers CD11b, CD13, CD14, CD45, EGR1, CSF1R, and IL-8 were assessed by
flow cytometry and RT-qPCR. Autophagy was monitored by RT-qPCR analysis of autophagy-related (ATG)
gene expression, LC3-II/p62 immunoblotting, beclin-1/Bcl-2 interaction, nuclear translocation of TFEB
and FOXO1/3. The activation of MAP kinases, ERK and JNK was assessed by immunoblotting. Pharmacological inhibition and RNA interference were used to determine the role of MAP kinases and autophagy
in HL60 cell differentiation.
Results: PMA-triggered differentiation of HL-60 cells into macrophage-like cells was confirmed by elevated expression of macrophage markers CD11b, CD13, CD14, CD45, EGR1, CSF1R, and IL-8. The induction of autophagy was demonstrated by accumulation/punctuation of LC3-II, and the increase in
autophagic flux. PMA also increased nuclear translocation of TFEB, FOXO1/3, as well asthe expression of
several ATG genesin HL-60 cells. PMA stimulated the phosphorylation of ERK and JNK via PKC-dependent
mechanism. Pharmacological or genetic inhibition of ERK or JNK suppressed PMA-triggered nuclear
translocation of TFEB and FOXO1/3, ATG expression, dissociation of beclin-1 from Bcl-2, autophagy induction, and differentiation of HL-60 cells into macrophage-like cells.
Conclusion: Our study revealed the involvement of ERK and JNK in TFEB/FOXO-dependent autophagy
and differentiation of HL60 cells, indicating MAP kinase-mediated autophagy as a possible target in differentiation therapy of AML.
PB  - Belgrade: Institute of Molecular Genetics and Genetic Engineering, University of Belgrade
C3  - Abstract Book: CoMBoS2 - the Second Congress of Molecular Biologists of Serbia; 2023 Oct 6-8; Belgrade, Serbia
T1  - MAP kinases activate TFEB/FOXO-dependent autophagy involved in phorbol myristate acetate-induced macrophage differentiation of HL-60 leukemia cells
SP  - 56
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_6285
ER  - 

@conference{
author = "Mandić, Miloš and Misirkić Marjanović, Maja and Vučićević, Ljubica and Bošnjak, Mihajlo and Perović, Vladimir and Ristić, Biljana and Ćirić, Darko and Janjetović, Kristina and Paunović, Verica and Stevanović, Danijela and Kosić, Milica and Harhaji-Trajković, Ljubica and Trajković, Vladimir",
year = "2023",
abstract = "Introduction: Autophagy has been shown to participate in the differentiation of hematopoietic and
leukemic cells. We investigated the mechanisms of autophagy action in the differentiation induced by
PKC activator phorbol myristate acetate (PMA) in HL-60 acute myeloid leukemia cells.
Methods: The macrophage markers CD11b, CD13, CD14, CD45, EGR1, CSF1R, and IL-8 were assessed by
flow cytometry and RT-qPCR. Autophagy was monitored by RT-qPCR analysis of autophagy-related (ATG)
gene expression, LC3-II/p62 immunoblotting, beclin-1/Bcl-2 interaction, nuclear translocation of TFEB
and FOXO1/3. The activation of MAP kinases, ERK and JNK was assessed by immunoblotting. Pharmacological inhibition and RNA interference were used to determine the role of MAP kinases and autophagy
in HL60 cell differentiation.
Results: PMA-triggered differentiation of HL-60 cells into macrophage-like cells was confirmed by elevated expression of macrophage markers CD11b, CD13, CD14, CD45, EGR1, CSF1R, and IL-8. The induction of autophagy was demonstrated by accumulation/punctuation of LC3-II, and the increase in
autophagic flux. PMA also increased nuclear translocation of TFEB, FOXO1/3, as well asthe expression of
several ATG genesin HL-60 cells. PMA stimulated the phosphorylation of ERK and JNK via PKC-dependent
mechanism. Pharmacological or genetic inhibition of ERK or JNK suppressed PMA-triggered nuclear
translocation of TFEB and FOXO1/3, ATG expression, dissociation of beclin-1 from Bcl-2, autophagy induction, and differentiation of HL-60 cells into macrophage-like cells.
Conclusion: Our study revealed the involvement of ERK and JNK in TFEB/FOXO-dependent autophagy
and differentiation of HL60 cells, indicating MAP kinase-mediated autophagy as a possible target in differentiation therapy of AML.",
publisher = "Belgrade: Institute of Molecular Genetics and Genetic Engineering, University of Belgrade",
journal = "Abstract Book: CoMBoS2 - the Second Congress of Molecular Biologists of Serbia; 2023 Oct 6-8; Belgrade, Serbia",
title = "MAP kinases activate TFEB/FOXO-dependent autophagy involved in phorbol myristate acetate-induced macrophage differentiation of HL-60 leukemia cells",
pages = "56",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_6285"
}

Mandić, M., Misirkić Marjanović, M., Vučićević, L., Bošnjak, M., Perović, V., Ristić, B., Ćirić, D., Janjetović, K., Paunović, V., Stevanović, D., Kosić, M., Harhaji-Trajković, L.,& Trajković, V.. (2023). MAP kinases activate TFEB/FOXO-dependent autophagy involved in phorbol myristate acetate-induced macrophage differentiation of HL-60 leukemia cells. in Abstract Book: CoMBoS2 - the Second Congress of Molecular Biologists of Serbia; 2023 Oct 6-8; Belgrade, Serbia
Belgrade: Institute of Molecular Genetics and Genetic Engineering, University of Belgrade., 56.
https://hdl.handle.net/21.15107/rcub_ibiss_6285

Mandić M, Misirkić Marjanović M, Vučićević L, Bošnjak M, Perović V, Ristić B, Ćirić D, Janjetović K, Paunović V, Stevanović D, Kosić M, Harhaji-Trajković L, Trajković V. MAP kinases activate TFEB/FOXO-dependent autophagy involved in phorbol myristate acetate-induced macrophage differentiation of HL-60 leukemia cells. in Abstract Book: CoMBoS2 - the Second Congress of Molecular Biologists of Serbia; 2023 Oct 6-8; Belgrade, Serbia. 2023;:56.
https://hdl.handle.net/21.15107/rcub_ibiss_6285 .

Mandić, Miloš, Misirkić Marjanović, Maja, Vučićević, Ljubica, Bošnjak, Mihajlo, Perović, Vladimir, Ristić, Biljana, Ćirić, Darko, Janjetović, Kristina, Paunović, Verica, Stevanović, Danijela, Kosić, Milica, Harhaji-Trajković, Ljubica, Trajković, Vladimir, "MAP kinases activate TFEB/FOXO-dependent autophagy involved in phorbol myristate acetate-induced macrophage differentiation of HL-60 leukemia cells" in Abstract Book: CoMBoS2 - the Second Congress of Molecular Biologists of Serbia; 2023 Oct 6-8; Belgrade, Serbia (2023):56,
https://hdl.handle.net/21.15107/rcub_ibiss_6285 .

TY  - JOUR
AU  - Ristić, Biljana
AU  - Bošnjak, Mihajlo
AU  - Misirkić Marjanović, Maja
AU  - Stevanović, Danijela
AU  - Janjetović, Kristina
AU  - Harhaji-Trajković, Ljubica
PY  - 2023
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6102
AB  - Graphene-based nanomaterials (GNMs), including graphene, graphene oxide, reduced
graphene oxide, and graphene quantum dots, may have direct anticancer activity or be used as
nanocarriers for antitumor drugs. GNMs usually enter tumor cells by endocytosis and can accumu late in lysosomes. This accumulation prevents drugs bound to GNMs from reaching their targets,
suppressing their anticancer effects. A number of chemical modifications are made to GNMs to
facilitate the separation of anticancer drugs from GNMs at low lysosomal pH and to enable the
lysosomal escape of drugs. Lysosomal escape may be associated with oxidative stress, permeabi lization of the unstable membrane of cancer cell lysosomes, release of lysosomal enzymes into the
cytoplasm, and cell death. GNMs can prevent or stimulate tumor cell death by inducing protective
autophagy or suppressing autolysosomal degradation, respectively. Furthermore, because GNMs
prevent bound fluorescent agents from emitting light, their separation in lysosomes may enable
tumor cell identification and therapy monitoring. In this review, we explain how the characteristics
of the lysosomal microenvironment and the unique features of tumor cell lysosomes can be exploited
for GNM-based cancer therapy.
PB  - Basel: MDPI
T2  - Pharmaceutics
T1  - The exploitation of lysosomes in cancer therapy with graphene-based nanomaterials
IS  - 7
VL  - 15
DO  - 10.3390/pharmaceutics15071846
SP  - 1846
ER  - 

@article{
author = "Ristić, Biljana and Bošnjak, Mihajlo and Misirkić Marjanović, Maja and Stevanović, Danijela and Janjetović, Kristina and Harhaji-Trajković, Ljubica",
year = "2023",
abstract = "Graphene-based nanomaterials (GNMs), including graphene, graphene oxide, reduced
graphene oxide, and graphene quantum dots, may have direct anticancer activity or be used as
nanocarriers for antitumor drugs. GNMs usually enter tumor cells by endocytosis and can accumu late in lysosomes. This accumulation prevents drugs bound to GNMs from reaching their targets,
suppressing their anticancer effects. A number of chemical modifications are made to GNMs to
facilitate the separation of anticancer drugs from GNMs at low lysosomal pH and to enable the
lysosomal escape of drugs. Lysosomal escape may be associated with oxidative stress, permeabi lization of the unstable membrane of cancer cell lysosomes, release of lysosomal enzymes into the
cytoplasm, and cell death. GNMs can prevent or stimulate tumor cell death by inducing protective
autophagy or suppressing autolysosomal degradation, respectively. Furthermore, because GNMs
prevent bound fluorescent agents from emitting light, their separation in lysosomes may enable
tumor cell identification and therapy monitoring. In this review, we explain how the characteristics
of the lysosomal microenvironment and the unique features of tumor cell lysosomes can be exploited
for GNM-based cancer therapy.",
publisher = "Basel: MDPI",
journal = "Pharmaceutics",
title = "The exploitation of lysosomes in cancer therapy with graphene-based nanomaterials",
number = "7",
volume = "15",
doi = "10.3390/pharmaceutics15071846",
pages = "1846"
}

Ristić, B., Bošnjak, M., Misirkić Marjanović, M., Stevanović, D., Janjetović, K.,& Harhaji-Trajković, L.. (2023). The exploitation of lysosomes in cancer therapy with graphene-based nanomaterials. in Pharmaceutics
Basel: MDPI., 15(7), 1846.
https://doi.org/10.3390/pharmaceutics15071846

Ristić B, Bošnjak M, Misirkić Marjanović M, Stevanović D, Janjetović K, Harhaji-Trajković L. The exploitation of lysosomes in cancer therapy with graphene-based nanomaterials. in Pharmaceutics. 2023;15(7):1846.
doi:10.3390/pharmaceutics15071846 .

Ristić, Biljana, Bošnjak, Mihajlo, Misirkić Marjanović, Maja, Stevanović, Danijela, Janjetović, Kristina, Harhaji-Trajković, Ljubica, "The exploitation of lysosomes in cancer therapy with graphene-based nanomaterials" in Pharmaceutics, 15, no. 7 (2023):1846,
https://doi.org/10.3390/pharmaceutics15071846 . .

TY  - JOUR
AU  - Despotović, Ana
AU  - Janjetović, Kristina
AU  - Zogović, Nevena
AU  - Tovilović-Kovačević, Gordana
PY  - 2023
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6302
AB  - Glioblastoma multiforme (GBM) is the most lethal primary brain tumor in adults, characterized by a highly invasive nature and therapy resistance. Combination of menadione and ascorbic acid (AA+MD) exerts strong ROS-mediated anti-GBM activity in vitro. The objective of this study was to improve AA+MD anti-GBM potential by modulating the activity of Akt and c-Jun N-terminal kinase (JNK), molecules with an important role in GBM development. The effects of Akt and JNK modulation on AA+MD toxicity in U251 human glioblastoma cells were assessed by cell viability assays, flow cytometry, RNA interference and plasmid overexpression, and immunoblot analysis. The AA+MD induced severe oxidative stress, an early increase in Akt phosphorylation followed by its strong inhibition, persistent JNK activation, and U251 cell death. Small molecule Akt kinase inhibitor 10-DEBC enhanced, while pharmacological and genetic Akt activation decreased, AA+MD-induced toxicity. The U251 cell death potentiation by 10-DEBC correlated with an increase in the combination-induced autophagic flux and was abolished by genetic autophagy silencing. Additionally, pharmacological JNK inhibitor SP600125 augmented combination toxicity toward U251 cells, an effect linked with increased ROS accumulation. These results indicate that small Akt and JNK kinase inhibitors significantly enhance AA+MD anti-GBM effects by autophagy potentiation and amplifying deleterious ROS levels.
PB  - Basel: MDPI
T2  - Biomedicines
T1  - Pharmacological Akt and JNK kinase inhibitors 10-DEBC and SP600125 potentiate anti-glioblastoma effect of menadione and ascorbic acid combination in human U251 glioblastoma cells
IS  - 10
VL  - 11
DO  - 10.3390/biomedicines11102652
SP  - 2652
ER  - 

@article{
author = "Despotović, Ana and Janjetović, Kristina and Zogović, Nevena and Tovilović-Kovačević, Gordana",
year = "2023",
abstract = "Glioblastoma multiforme (GBM) is the most lethal primary brain tumor in adults, characterized by a highly invasive nature and therapy resistance. Combination of menadione and ascorbic acid (AA+MD) exerts strong ROS-mediated anti-GBM activity in vitro. The objective of this study was to improve AA+MD anti-GBM potential by modulating the activity of Akt and c-Jun N-terminal kinase (JNK), molecules with an important role in GBM development. The effects of Akt and JNK modulation on AA+MD toxicity in U251 human glioblastoma cells were assessed by cell viability assays, flow cytometry, RNA interference and plasmid overexpression, and immunoblot analysis. The AA+MD induced severe oxidative stress, an early increase in Akt phosphorylation followed by its strong inhibition, persistent JNK activation, and U251 cell death. Small molecule Akt kinase inhibitor 10-DEBC enhanced, while pharmacological and genetic Akt activation decreased, AA+MD-induced toxicity. The U251 cell death potentiation by 10-DEBC correlated with an increase in the combination-induced autophagic flux and was abolished by genetic autophagy silencing. Additionally, pharmacological JNK inhibitor SP600125 augmented combination toxicity toward U251 cells, an effect linked with increased ROS accumulation. These results indicate that small Akt and JNK kinase inhibitors significantly enhance AA+MD anti-GBM effects by autophagy potentiation and amplifying deleterious ROS levels.",
publisher = "Basel: MDPI",
journal = "Biomedicines",
title = "Pharmacological Akt and JNK kinase inhibitors 10-DEBC and SP600125 potentiate anti-glioblastoma effect of menadione and ascorbic acid combination in human U251 glioblastoma cells",
number = "10",
volume = "11",
doi = "10.3390/biomedicines11102652",
pages = "2652"
}

Despotović, A., Janjetović, K., Zogović, N.,& Tovilović-Kovačević, G.. (2023). Pharmacological Akt and JNK kinase inhibitors 10-DEBC and SP600125 potentiate anti-glioblastoma effect of menadione and ascorbic acid combination in human U251 glioblastoma cells. in Biomedicines
Basel: MDPI., 11(10), 2652.
https://doi.org/10.3390/biomedicines11102652

Despotović A, Janjetović K, Zogović N, Tovilović-Kovačević G. Pharmacological Akt and JNK kinase inhibitors 10-DEBC and SP600125 potentiate anti-glioblastoma effect of menadione and ascorbic acid combination in human U251 glioblastoma cells. in Biomedicines. 2023;11(10):2652.
doi:10.3390/biomedicines11102652 .

Despotović, Ana, Janjetović, Kristina, Zogović, Nevena, Tovilović-Kovačević, Gordana, "Pharmacological Akt and JNK kinase inhibitors 10-DEBC and SP600125 potentiate anti-glioblastoma effect of menadione and ascorbic acid combination in human U251 glioblastoma cells" in Biomedicines, 11, no. 10 (2023):2652,
https://doi.org/10.3390/biomedicines11102652 . .

TY  - JOUR
AU  - Božinović, Nevena
AU  - Savva, Kyriaki
AU  - Rajić, Vladimir
AU  - Popović, Maja
AU  - Tošić, Dragana
AU  - Janjetović, Kristina
AU  - Despotović, Ana
AU  - Zogović, Nevena
AU  - Stratakis, Emmanuel
AU  - Petrović, Suzana
PY  - 2023
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6271
AB  - The creation of novel biocompatible Ti-based thin films with a Zr or Cu sub-layer modified by ultrafast laser processing is studied. To prepare bioactive surfaces, ultrafast laser processing is focused on the formation of laser-induced periodic surface structures (LIPSS) with the production of oxide phases at the surfaces. Two differently designed multilayer thin films Ti/Cu/Ti and Ti/Zr/Ti were deposited on the silicon using the ion sputtering method. The Ti thin film contains Cu or Zr sub-layer (thickness of 10 nm) at the 10 nm below the surface. The composition and surface morphology variations for these systems, deposited and laser-processed under the same experimental conditions, were caused only by different thermo-physical properties of the sub-layer (Cu or Zr). The surface morphology in the form of LIPSS, led to improved cell adhesion and stable cells/thin films interface compared to as-deposited samples. Field-emission scanning electron microscopy and MTT analysis revealed that laser processing of both systems increased cell adhesion, proliferation, and metabolical activity of L929 mouse fibroblast cells compared to non-modified flat surfaces. Overall, the biocompatibility of Zr-containing thin films is better than Ti/Cu/Ti system. Further, laser processing and formation of LIPSS makes Ti/Zr/Ti thin films excellent candidate for biomedical.
PB  - Amsterdam: Elsevier
T2  - Materials Chemistry and Physics
T1  - Influence of zirconium and copper sub-layer in cell integrations on femtosecond laser-processed Ti thin films
VL  - 308
DO  - 10.1016/j.matchemphys.2023.128286
SP  - 128286
ER  - 

@article{
author = "Božinović, Nevena and Savva, Kyriaki and Rajić, Vladimir and Popović, Maja and Tošić, Dragana and Janjetović, Kristina and Despotović, Ana and Zogović, Nevena and Stratakis, Emmanuel and Petrović, Suzana",
year = "2023",
abstract = "The creation of novel biocompatible Ti-based thin films with a Zr or Cu sub-layer modified by ultrafast laser processing is studied. To prepare bioactive surfaces, ultrafast laser processing is focused on the formation of laser-induced periodic surface structures (LIPSS) with the production of oxide phases at the surfaces. Two differently designed multilayer thin films Ti/Cu/Ti and Ti/Zr/Ti were deposited on the silicon using the ion sputtering method. The Ti thin film contains Cu or Zr sub-layer (thickness of 10 nm) at the 10 nm below the surface. The composition and surface morphology variations for these systems, deposited and laser-processed under the same experimental conditions, were caused only by different thermo-physical properties of the sub-layer (Cu or Zr). The surface morphology in the form of LIPSS, led to improved cell adhesion and stable cells/thin films interface compared to as-deposited samples. Field-emission scanning electron microscopy and MTT analysis revealed that laser processing of both systems increased cell adhesion, proliferation, and metabolical activity of L929 mouse fibroblast cells compared to non-modified flat surfaces. Overall, the biocompatibility of Zr-containing thin films is better than Ti/Cu/Ti system. Further, laser processing and formation of LIPSS makes Ti/Zr/Ti thin films excellent candidate for biomedical.",
publisher = "Amsterdam: Elsevier",
journal = "Materials Chemistry and Physics",
title = "Influence of zirconium and copper sub-layer in cell integrations on femtosecond laser-processed Ti thin films",
volume = "308",
doi = "10.1016/j.matchemphys.2023.128286",
pages = "128286"
}

Božinović, N., Savva, K., Rajić, V., Popović, M., Tošić, D., Janjetović, K., Despotović, A., Zogović, N., Stratakis, E.,& Petrović, S.. (2023). Influence of zirconium and copper sub-layer in cell integrations on femtosecond laser-processed Ti thin films. in Materials Chemistry and Physics
Amsterdam: Elsevier., 308, 128286.
https://doi.org/10.1016/j.matchemphys.2023.128286

Božinović N, Savva K, Rajić V, Popović M, Tošić D, Janjetović K, Despotović A, Zogović N, Stratakis E, Petrović S. Influence of zirconium and copper sub-layer in cell integrations on femtosecond laser-processed Ti thin films. in Materials Chemistry and Physics. 2023;308:128286.
doi:10.1016/j.matchemphys.2023.128286 .

Božinović, Nevena, Savva, Kyriaki, Rajić, Vladimir, Popović, Maja, Tošić, Dragana, Janjetović, Kristina, Despotović, Ana, Zogović, Nevena, Stratakis, Emmanuel, Petrović, Suzana, "Influence of zirconium and copper sub-layer in cell integrations on femtosecond laser-processed Ti thin films" in Materials Chemistry and Physics, 308 (2023):128286,
https://doi.org/10.1016/j.matchemphys.2023.128286 . .

TY  - CONF
AU  - Dožić, Aleksandra
AU  - Ćetković, Dejan
AU  - Despotović, Ana
AU  - Janjetović, Kristina
AU  - Zogović, Nevena
AU  - Antonijević, Đorđe
PY  - 2022
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5739
AB  - The aim of this study was to investigate the properties of experimental calcium aluminate (CA) dental cement, synthesized from CaO×Al2O3 and CaCO3. Calcium silicate (Portland cement, PC) served as a control. The elastic modulus and maximum stress obtained using the universal testing machine showed that CA has greater mechanical resistance than the control PC. Scanning electron microscopy (SEM) analysis of cements specimens before and after soaking in phosphate buffer saline showed that hydrated cements exposed crystal particles of calcite and new aluminum containing phases on their surfaces, suggesting their bioactive potential. Biocompatibility of the CA dental cement was evaluated by observing L929 cells morphology using phase-contrast microscopy. Cells treated with CA extract preserved their structural integrity without any changes in cell morphology, but with a slightly inhibited proliferation rate after 24h treatment, while PC induced changes typical for cell death.
PB  - Belgrade: Society of Physical Chemists of Serbia
C3  - Proceedings: 16th International Conference on Fundamental and Applied Aspects of Physical Chemistry: Physical Chemistry 2022, Vol. 2; 2022 Sep 26-30; Belgrade, Serbia
T1  - Surface morphology, compressive strength and biocompatibility of calcium aluminate dental cement
SP  - 327
EP  - 330
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5739
ER  - 

@conference{
author = "Dožić, Aleksandra and Ćetković, Dejan and Despotović, Ana and Janjetović, Kristina and Zogović, Nevena and Antonijević, Đorđe",
year = "2022",
abstract = "The aim of this study was to investigate the properties of experimental calcium aluminate (CA) dental cement, synthesized from CaO×Al2O3 and CaCO3. Calcium silicate (Portland cement, PC) served as a control. The elastic modulus and maximum stress obtained using the universal testing machine showed that CA has greater mechanical resistance than the control PC. Scanning electron microscopy (SEM) analysis of cements specimens before and after soaking in phosphate buffer saline showed that hydrated cements exposed crystal particles of calcite and new aluminum containing phases on their surfaces, suggesting their bioactive potential. Biocompatibility of the CA dental cement was evaluated by observing L929 cells morphology using phase-contrast microscopy. Cells treated with CA extract preserved their structural integrity without any changes in cell morphology, but with a slightly inhibited proliferation rate after 24h treatment, while PC induced changes typical for cell death.",
publisher = "Belgrade: Society of Physical Chemists of Serbia",
journal = "Proceedings: 16th International Conference on Fundamental and Applied Aspects of Physical Chemistry: Physical Chemistry 2022, Vol. 2; 2022 Sep 26-30; Belgrade, Serbia",
title = "Surface morphology, compressive strength and biocompatibility of calcium aluminate dental cement",
pages = "327-330",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5739"
}

Dožić, A., Ćetković, D., Despotović, A., Janjetović, K., Zogović, N.,& Antonijević, Đ.. (2022). Surface morphology, compressive strength and biocompatibility of calcium aluminate dental cement. in Proceedings: 16th International Conference on Fundamental and Applied Aspects of Physical Chemistry: Physical Chemistry 2022, Vol. 2; 2022 Sep 26-30; Belgrade, Serbia
Belgrade: Society of Physical Chemists of Serbia., 327-330.
https://hdl.handle.net/21.15107/rcub_ibiss_5739

Dožić A, Ćetković D, Despotović A, Janjetović K, Zogović N, Antonijević Đ. Surface morphology, compressive strength and biocompatibility of calcium aluminate dental cement. in Proceedings: 16th International Conference on Fundamental and Applied Aspects of Physical Chemistry: Physical Chemistry 2022, Vol. 2; 2022 Sep 26-30; Belgrade, Serbia. 2022;:327-330.
https://hdl.handle.net/21.15107/rcub_ibiss_5739 .

Dožić, Aleksandra, Ćetković, Dejan, Despotović, Ana, Janjetović, Kristina, Zogović, Nevena, Antonijević, Đorđe, "Surface morphology, compressive strength and biocompatibility of calcium aluminate dental cement" in Proceedings: 16th International Conference on Fundamental and Applied Aspects of Physical Chemistry: Physical Chemistry 2022, Vol. 2; 2022 Sep 26-30; Belgrade, Serbia (2022):327-330,
https://hdl.handle.net/21.15107/rcub_ibiss_5739 .

TY  - CONF
AU  - Janjetović, Kristina
AU  - Stamenković, Marina
AU  - Tovilović-Kovačević, Gordana
AU  - Zogović, Nevena
AU  - Despotović, Ana
AU  - Stevanović, Danijela
AU  - Mandić, Miloš
AU  - Kosić, Milica
AU  - Paunović, Verica
AU  - Vučićević, Ljubica
AU  - Misirkić Marjanović, Maja
AU  - Trajković, Vladimir
PY  - 2022
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5737
AB  - I pored stalnog napretka lečenja kancera, ova bolest ostaje druga po smrtnosti u svetu. Kako bi se skratio vremenski i finansijski zahtevan proces razvoja novih hemoterapeutika poslednjih desetak godina intezivno se radi na ispitivanju antikancerskog potencijala lekova koji se već koriste u terapiji drugih bolesti. U ovom radu smo proučavali potencijalni antikancerski efekat inhibitora protonske pumpe pantoprazola (PPZ), terapeutika koji se standardno koristi u lečenju kiselinskih gastrointestinalnih poremećaja. Citotoksični efekat PPZ je ispitivan u kulturama humanog U251 glioblastoma, humanog H460 nesitnoćelijskog karcinoma pluća i mišjeg B16 melanoma. Pokazano je da PPZ aktiviranoj apoptozi u svim ispitivanim ćelijskim linijama prethodi povećana produkcija reaktivnih vrsta kiseonika, depolarizacija mitohondrija i aktivacija kaspaza. U prisustvu PPZ detektovano je povećanje LC3 II proteina ukazujući na aktivaciju autofagije. Detaljnijim ispitivanjem mehanizma koji je u osnovi toksičnog efekta PPZ, utvrđeno je da PPZ aktivira AKT/AMPK signalni put u ispitivanim ćelijskim linijama i stimuliše AMPK zavisnu citoprotektivnu autofagiju u U251 i B16 ćelijskim linijama. Sa druge strane, autofagija aktivirana u ćelijama karcinoma pluća je citotoksična. Sumirano, PPZ ispoljava značajan antikancerski potencijal prema U251, H460 i B16 ćelijama izazivajući apoptozu, pri čemu uloga autofagije u smrti ćelija može biti citoprotektivna ili citotoksična i zavisi od tipa ćelija. Dodatna farmakološka modulacija autofagije mogla bi poboljšati antikancerski potencijal pantoprazola.
AB  - И поред сталног напретка лечења канцера, ова болест остаје друга по смртности у
свету. Како би се скратио временски и финансијски захтеван процес развоја нових
хемотерапеутика последњих десетак година интезивно се ради на испитивању
антиканцерског потенцијала лекова који се већ користе у терапији других болести.
У овом раду смо проучавали потенцијални антиканцерски ефекат инхибитора
протонске пумпе пантопразола (ППЗ), терапеутика који се стандардно користи у
лечењу киселинских гастроинтестиналних поремећаја. Цитотоксични ефекат ППЗ
је испитиван у културама хуманог U251 глиобластома, хуманог H460
неситноћелијског карцинома плућа и мишјег B16 меланома. Показано је да ППЗ
активираној апоптози у свим испитиваним ћелијским линијама претходи повећана
продукција реактивних врста кисеоника, деполаризација митохондрија и
активација каспаза. У присуству ППЗ детектовано је повећање LC3 II протеина
указујући на активацију аутофагије. Детаљнијим испитивањем механизма који је у
основи токсичног ефекта ППЗ, утврђено је да ППЗ активира AKT/AMPK сигнални
пут у испитиваним ћелијским линијама и стимулише AMPK зависну
цитопротективну аутофагију у U251 и B16 ћелијским линијама. Са друге стране,
аутофагија активирана у ћелијама карцинома плућа је цитотоксична. Сумирано,
ППЗ испољава значајан антиканцерски потенцијал према U251, H460 и B16
ћелијама изазивајући апоптозу, при чему улога аутофагије у смрти ћелија може
бити цитопротективна или цитотоксична и зависи од типа ћелија. Додатна
фармаколошка модулација аутофагије могла би побољшати антиканцерски
потенцијал пантопразола.
PB  - Belgrade: Serbian Biological Society
C3  - Knjiga sažetaka: Treći Kongres biologa Srbije: Osnovna i primenjena istraživanja: Metodika nastave; 2022 Sep 21-25; Zlatibor, Serbia
T1  - Antikancerski potencijal inhibitora protonske pumpe pantoprazola
T1  - Антиканцерски потенцијал инхибитора протонске пумпе пантопразола
SP  - 285
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5737
ER  - 

@conference{
author = "Janjetović, Kristina and Stamenković, Marina and Tovilović-Kovačević, Gordana and Zogović, Nevena and Despotović, Ana and Stevanović, Danijela and Mandić, Miloš and Kosić, Milica and Paunović, Verica and Vučićević, Ljubica and Misirkić Marjanović, Maja and Trajković, Vladimir",
year = "2022",
abstract = "I pored stalnog napretka lečenja kancera, ova bolest ostaje druga po smrtnosti u svetu. Kako bi se skratio vremenski i finansijski zahtevan proces razvoja novih hemoterapeutika poslednjih desetak godina intezivno se radi na ispitivanju antikancerskog potencijala lekova koji se već koriste u terapiji drugih bolesti. U ovom radu smo proučavali potencijalni antikancerski efekat inhibitora protonske pumpe pantoprazola (PPZ), terapeutika koji se standardno koristi u lečenju kiselinskih gastrointestinalnih poremećaja. Citotoksični efekat PPZ je ispitivan u kulturama humanog U251 glioblastoma, humanog H460 nesitnoćelijskog karcinoma pluća i mišjeg B16 melanoma. Pokazano je da PPZ aktiviranoj apoptozi u svim ispitivanim ćelijskim linijama prethodi povećana produkcija reaktivnih vrsta kiseonika, depolarizacija mitohondrija i aktivacija kaspaza. U prisustvu PPZ detektovano je povećanje LC3 II proteina ukazujući na aktivaciju autofagije. Detaljnijim ispitivanjem mehanizma koji je u osnovi toksičnog efekta PPZ, utvrđeno je da PPZ aktivira AKT/AMPK signalni put u ispitivanim ćelijskim linijama i stimuliše AMPK zavisnu citoprotektivnu autofagiju u U251 i B16 ćelijskim linijama. Sa druge strane, autofagija aktivirana u ćelijama karcinoma pluća je citotoksična. Sumirano, PPZ ispoljava značajan antikancerski potencijal prema U251, H460 i B16 ćelijama izazivajući apoptozu, pri čemu uloga autofagije u smrti ćelija može biti citoprotektivna ili citotoksična i zavisi od tipa ćelija. Dodatna farmakološka modulacija autofagije mogla bi poboljšati antikancerski potencijal pantoprazola., И поред сталног напретка лечења канцера, ова болест остаје друга по смртности у
свету. Како би се скратио временски и финансијски захтеван процес развоја нових
хемотерапеутика последњих десетак година интезивно се ради на испитивању
антиканцерског потенцијала лекова који се већ користе у терапији других болести.
У овом раду смо проучавали потенцијални антиканцерски ефекат инхибитора
протонске пумпе пантопразола (ППЗ), терапеутика који се стандардно користи у
лечењу киселинских гастроинтестиналних поремећаја. Цитотоксични ефекат ППЗ
је испитиван у културама хуманог U251 глиобластома, хуманог H460
неситноћелијског карцинома плућа и мишјег B16 меланома. Показано је да ППЗ
активираној апоптози у свим испитиваним ћелијским линијама претходи повећана
продукција реактивних врста кисеоника, деполаризација митохондрија и
активација каспаза. У присуству ППЗ детектовано је повећање LC3 II протеина
указујући на активацију аутофагије. Детаљнијим испитивањем механизма који је у
основи токсичног ефекта ППЗ, утврђено је да ППЗ активира AKT/AMPK сигнални
пут у испитиваним ћелијским линијама и стимулише AMPK зависну
цитопротективну аутофагију у U251 и B16 ћелијским линијама. Са друге стране,
аутофагија активирана у ћелијама карцинома плућа је цитотоксична. Сумирано,
ППЗ испољава значајан антиканцерски потенцијал према U251, H460 и B16
ћелијама изазивајући апоптозу, при чему улога аутофагије у смрти ћелија може
бити цитопротективна или цитотоксична и зависи од типа ћелија. Додатна
фармаколошка модулација аутофагије могла би побољшати антиканцерски
потенцијал пантопразола.",
publisher = "Belgrade: Serbian Biological Society",
journal = "Knjiga sažetaka: Treći Kongres biologa Srbije: Osnovna i primenjena istraživanja: Metodika nastave; 2022 Sep 21-25; Zlatibor, Serbia",
title = "Antikancerski potencijal inhibitora protonske pumpe pantoprazola, Антиканцерски потенцијал инхибитора протонске пумпе пантопразола",
pages = "285",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5737"
}

Janjetović, K., Stamenković, M., Tovilović-Kovačević, G., Zogović, N., Despotović, A., Stevanović, D., Mandić, M., Kosić, M., Paunović, V., Vučićević, L., Misirkić Marjanović, M.,& Trajković, V.. (2022). Antikancerski potencijal inhibitora protonske pumpe pantoprazola. in Knjiga sažetaka: Treći Kongres biologa Srbije: Osnovna i primenjena istraživanja: Metodika nastave; 2022 Sep 21-25; Zlatibor, Serbia
Belgrade: Serbian Biological Society., 285.
https://hdl.handle.net/21.15107/rcub_ibiss_5737

Janjetović K, Stamenković M, Tovilović-Kovačević G, Zogović N, Despotović A, Stevanović D, Mandić M, Kosić M, Paunović V, Vučićević L, Misirkić Marjanović M, Trajković V. Antikancerski potencijal inhibitora protonske pumpe pantoprazola. in Knjiga sažetaka: Treći Kongres biologa Srbije: Osnovna i primenjena istraživanja: Metodika nastave; 2022 Sep 21-25; Zlatibor, Serbia. 2022;:285.
https://hdl.handle.net/21.15107/rcub_ibiss_5737 .

Janjetović, Kristina, Stamenković, Marina, Tovilović-Kovačević, Gordana, Zogović, Nevena, Despotović, Ana, Stevanović, Danijela, Mandić, Miloš, Kosić, Milica, Paunović, Verica, Vučićević, Ljubica, Misirkić Marjanović, Maja, Trajković, Vladimir, "Antikancerski potencijal inhibitora protonske pumpe pantoprazola" in Knjiga sažetaka: Treći Kongres biologa Srbije: Osnovna i primenjena istraživanja: Metodika nastave; 2022 Sep 21-25; Zlatibor, Serbia (2022):285,
https://hdl.handle.net/21.15107/rcub_ibiss_5737 .

TY  - CONF
AU  - Ćetković, Dejan
AU  - Dožić, Aleksandra
AU  - Despotović, Ana
AU  - Janjetović, Kristina
AU  - Zogović, Nevena
AU  - Antonijević, Đorđe
PY  - 2022
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5738
AB  - This study aimed to investigate the influence of ZrO2, Bi2O3 and SrF2 added as radiopacifying agents (30wt.%) into calcium silicate/hydroxyapatite-based dental cement on its physical and biological properties. Among investigated cements, the mixture containing Bi2O3 had the highest values of elastic modules and toughness, similarly to control – mineral trioxide aggregate (MTA). SEM analysis of all hydrated cements has shown that bioactive calcite and tobermorite phases were formed. Crystal violet assay showed that pure (undiluted) extracts of experimental cements did not affect cell viability, while MTA exhibited an extremely cytotoxic effect on L929 cells. In 1:4 dilutions all experimental mixtures significantly increased cell proliferation potential after 72h in comparison to untreated cells and MTA, which cytotoxic effect diminished with dilutions. Further studies are needed to determine which radiopacifyer has the most desirable properties for adequate dental cement fabrication.
PB  - Belgrade: Society of Physical Chemists of Serbia
C3  - Proceedings: 16th International Conference on Fundamental and Applied Aspects of Physical Chemistry: Physical Chemistry 2022, Vol. 2; 2022 Sep 26-30; Belgrade, Serbia
T1  - Effect of various radiopacifiers on selected physical properties and cytotoxicity of calcium silicate based dental cement enriched with hydroxyapatite
SP  - 323
EP  - 326
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5738
ER  - 

@conference{
author = "Ćetković, Dejan and Dožić, Aleksandra and Despotović, Ana and Janjetović, Kristina and Zogović, Nevena and Antonijević, Đorđe",
year = "2022",
abstract = "This study aimed to investigate the influence of ZrO2, Bi2O3 and SrF2 added as radiopacifying agents (30wt.%) into calcium silicate/hydroxyapatite-based dental cement on its physical and biological properties. Among investigated cements, the mixture containing Bi2O3 had the highest values of elastic modules and toughness, similarly to control – mineral trioxide aggregate (MTA). SEM analysis of all hydrated cements has shown that bioactive calcite and tobermorite phases were formed. Crystal violet assay showed that pure (undiluted) extracts of experimental cements did not affect cell viability, while MTA exhibited an extremely cytotoxic effect on L929 cells. In 1:4 dilutions all experimental mixtures significantly increased cell proliferation potential after 72h in comparison to untreated cells and MTA, which cytotoxic effect diminished with dilutions. Further studies are needed to determine which radiopacifyer has the most desirable properties for adequate dental cement fabrication.",
publisher = "Belgrade: Society of Physical Chemists of Serbia",
journal = "Proceedings: 16th International Conference on Fundamental and Applied Aspects of Physical Chemistry: Physical Chemistry 2022, Vol. 2; 2022 Sep 26-30; Belgrade, Serbia",
title = "Effect of various radiopacifiers on selected physical properties and cytotoxicity of calcium silicate based dental cement enriched with hydroxyapatite",
pages = "323-326",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5738"
}

Ćetković, D., Dožić, A., Despotović, A., Janjetović, K., Zogović, N.,& Antonijević, Đ.. (2022). Effect of various radiopacifiers on selected physical properties and cytotoxicity of calcium silicate based dental cement enriched with hydroxyapatite. in Proceedings: 16th International Conference on Fundamental and Applied Aspects of Physical Chemistry: Physical Chemistry 2022, Vol. 2; 2022 Sep 26-30; Belgrade, Serbia
Belgrade: Society of Physical Chemists of Serbia., 323-326.
https://hdl.handle.net/21.15107/rcub_ibiss_5738

Ćetković D, Dožić A, Despotović A, Janjetović K, Zogović N, Antonijević Đ. Effect of various radiopacifiers on selected physical properties and cytotoxicity of calcium silicate based dental cement enriched with hydroxyapatite. in Proceedings: 16th International Conference on Fundamental and Applied Aspects of Physical Chemistry: Physical Chemistry 2022, Vol. 2; 2022 Sep 26-30; Belgrade, Serbia. 2022;:323-326.
https://hdl.handle.net/21.15107/rcub_ibiss_5738 .

Ćetković, Dejan, Dožić, Aleksandra, Despotović, Ana, Janjetović, Kristina, Zogović, Nevena, Antonijević, Đorđe, "Effect of various radiopacifiers on selected physical properties and cytotoxicity of calcium silicate based dental cement enriched with hydroxyapatite" in Proceedings: 16th International Conference on Fundamental and Applied Aspects of Physical Chemistry: Physical Chemistry 2022, Vol. 2; 2022 Sep 26-30; Belgrade, Serbia (2022):323-326,
https://hdl.handle.net/21.15107/rcub_ibiss_5738 .

TY  - CONF
AU  - Kosić, Milica
AU  - Paunović, Verica
AU  - Ristić, Biljana
AU  - Mirčić, Aleksandar
AU  - Bošnjak, Mihajlo
AU  - Stevanović, Danijela
AU  - Mandić, Miloš
AU  - Stamenković, Marina
AU  - Janjetović, Kristina
AU  - Vučićević, Ljubica
AU  - Trajković, Vladimir
AU  - Harhaji-Trajković, Ljubica
PY  - 2021
UR  - https://www.sfrre2021belgrade.rs/
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/4727
AB  - There is no effective therapy for melanoma, a malignant tumor of melanocytes with an
increasing incidence. High energy demands of melanoma cells are predominantly satisfied by
aerobic glycolysis. When glycolysis is suppressed, these metabolically plastic cells switch to
oxidative phosphorylation. The aim of this study was to investigate the antimelanoma effects of
simultaneous inhibition of glycolysis by 2-deoxy-D-glucose (2DG) and oxidative phosphorylation
by rotenone (ROT). 2DG synergized with ROT in inducing death of B16 melanoma, but not
primary mesenchymal cells. Combined treatment stimulated caspase activation, but not PARP
cleavage and DNA fragmentation. Disintegration of plasma membrane and inability of caspase
inhibitors and necrostatin to suppress toxicity of 2DG/ROT implied that combined treatment
induced necrosis, rather than apoptosis and necroptosis. 2DG/ROT stimulated ATP depletion,
mitochondrial superoxide production, and mitochondrial swelling, but not depolarization
of mitochondria. 2DG/ROT-induced toxicity was suppressed by antioxidant α-tocopherol,
but not mitochondrial depolarization inhibitor cyclosporine. Combined treatment induced
the translocation of hexokinase II, a suppressor of voltage-dependent anion channel (VDAC)
opening, and cytochrome c from mitochondria in the cytoplasm, while VDAC opening inhibitor
DIDS suppressed 2DG/ROT toxicity. Our results suggest that 2DG/ROT treatment stimulates
mitochondrial swelling, release of hexokinase II and subsequent opening of VDAC in the outer
mitochondrial membrane. These events allow cytochrome c to exit and activate caspases, which
are unable to stimulate PARP and consequent DNA fragmentation in the energy-depleted state.
On the other hand, superoxide synthesized in mitochondria upon 2DG/ROT treatment also exits
through VDAC and triggers energy-independent necrosis. Simultaneous inhibition of glycolysis
and oxidative phosphorylation appears to be promising strategy for further development of
novel anticancer therapeutics.
PB  - Elsevier Inc.
C3  - Free Radical Research Europe (SFRR-E) Annual Meeting Abstracts “Redox biology in the 21st century: a new scientific discipline” 15-18 June 2021, Belgrade, Serbia
T1  - Synergistic anticancer effect of glycolysis inhibition and oxidative phosphorylation suppression
DO  - 10.1016/j.freeradbiomed.2021.08.205
SP  - 203
ER  - 

@conference{
author = "Kosić, Milica and Paunović, Verica and Ristić, Biljana and Mirčić, Aleksandar and Bošnjak, Mihajlo and Stevanović, Danijela and Mandić, Miloš and Stamenković, Marina and Janjetović, Kristina and Vučićević, Ljubica and Trajković, Vladimir and Harhaji-Trajković, Ljubica",
year = "2021",
abstract = "There is no effective therapy for melanoma, a malignant tumor of melanocytes with an
increasing incidence. High energy demands of melanoma cells are predominantly satisfied by
aerobic glycolysis. When glycolysis is suppressed, these metabolically plastic cells switch to
oxidative phosphorylation. The aim of this study was to investigate the antimelanoma effects of
simultaneous inhibition of glycolysis by 2-deoxy-D-glucose (2DG) and oxidative phosphorylation
by rotenone (ROT). 2DG synergized with ROT in inducing death of B16 melanoma, but not
primary mesenchymal cells. Combined treatment stimulated caspase activation, but not PARP
cleavage and DNA fragmentation. Disintegration of plasma membrane and inability of caspase
inhibitors and necrostatin to suppress toxicity of 2DG/ROT implied that combined treatment
induced necrosis, rather than apoptosis and necroptosis. 2DG/ROT stimulated ATP depletion,
mitochondrial superoxide production, and mitochondrial swelling, but not depolarization
of mitochondria. 2DG/ROT-induced toxicity was suppressed by antioxidant α-tocopherol,
but not mitochondrial depolarization inhibitor cyclosporine. Combined treatment induced
the translocation of hexokinase II, a suppressor of voltage-dependent anion channel (VDAC)
opening, and cytochrome c from mitochondria in the cytoplasm, while VDAC opening inhibitor
DIDS suppressed 2DG/ROT toxicity. Our results suggest that 2DG/ROT treatment stimulates
mitochondrial swelling, release of hexokinase II and subsequent opening of VDAC in the outer
mitochondrial membrane. These events allow cytochrome c to exit and activate caspases, which
are unable to stimulate PARP and consequent DNA fragmentation in the energy-depleted state.
On the other hand, superoxide synthesized in mitochondria upon 2DG/ROT treatment also exits
through VDAC and triggers energy-independent necrosis. Simultaneous inhibition of glycolysis
and oxidative phosphorylation appears to be promising strategy for further development of
novel anticancer therapeutics.",
publisher = "Elsevier Inc.",
journal = "Free Radical Research Europe (SFRR-E) Annual Meeting Abstracts “Redox biology in the 21st century: a new scientific discipline” 15-18 June 2021, Belgrade, Serbia",
title = "Synergistic anticancer effect of glycolysis inhibition and oxidative phosphorylation suppression",
doi = "10.1016/j.freeradbiomed.2021.08.205",
pages = "203"
}

Kosić, M., Paunović, V., Ristić, B., Mirčić, A., Bošnjak, M., Stevanović, D., Mandić, M., Stamenković, M., Janjetović, K., Vučićević, L., Trajković, V.,& Harhaji-Trajković, L.. (2021). Synergistic anticancer effect of glycolysis inhibition and oxidative phosphorylation suppression. in Free Radical Research Europe (SFRR-E) Annual Meeting Abstracts “Redox biology in the 21st century: a new scientific discipline” 15-18 June 2021, Belgrade, Serbia
Elsevier Inc.., 203.
https://doi.org/10.1016/j.freeradbiomed.2021.08.205

Kosić M, Paunović V, Ristić B, Mirčić A, Bošnjak M, Stevanović D, Mandić M, Stamenković M, Janjetović K, Vučićević L, Trajković V, Harhaji-Trajković L. Synergistic anticancer effect of glycolysis inhibition and oxidative phosphorylation suppression. in Free Radical Research Europe (SFRR-E) Annual Meeting Abstracts “Redox biology in the 21st century: a new scientific discipline” 15-18 June 2021, Belgrade, Serbia. 2021;:203.
doi:10.1016/j.freeradbiomed.2021.08.205 .

Kosić, Milica, Paunović, Verica, Ristić, Biljana, Mirčić, Aleksandar, Bošnjak, Mihajlo, Stevanović, Danijela, Mandić, Miloš, Stamenković, Marina, Janjetović, Kristina, Vučićević, Ljubica, Trajković, Vladimir, Harhaji-Trajković, Ljubica, "Synergistic anticancer effect of glycolysis inhibition and oxidative phosphorylation suppression" in Free Radical Research Europe (SFRR-E) Annual Meeting Abstracts “Redox biology in the 21st century: a new scientific discipline” 15-18 June 2021, Belgrade, Serbia (2021):203,
https://doi.org/10.1016/j.freeradbiomed.2021.08.205 . .

TY  - CONF
AU  - Harhaji-Trajković, Ljubica
AU  - Kosić, Milica
AU  - Paunović, Verica
AU  - Ristić, Biljana
AU  - Bošnjak, Mihajlo
AU  - Zogović, Nevena
AU  - Mandić, Miloš
AU  - Tovilović-Kovačević, Gordana
AU  - Janjetović, Kristina
AU  - Trajković, Vladimir
PY  - 2021
UR  - https://www.sdir.ac.rs/apstrakti-SDIR-5/
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/4709
AB  - Background: Intensive proliferation of tumor cells consumes a lot of energy. In nutrient deficiency 
substrates for energy metabolism are obtained by lysosomal degradation of unnecessary/dysfunctional 
intracellular organelles/molecules in the process of autophagy. Leakage of enlarged unstable lysosomes, 
which characterize tumor cells, causes cell death. We investigated antitumor effect of combined targeting 
of lysosomes/autophagy and energy metabolism. Material and Methods: Toxicity against U251 human 
glioma and B16 mouse melanoma cells was measured by viability tests. Type/mechanisms of cell death 
were determined by flow cytometry, immunoblot, fluorescent/electron microscopy and confirmed by 
appropriate genetic/pharmacological inhibitors. Therapeutic potential was estimated in B16 melanoma bearing C57Bl/6 mice. Results: In the first study, lysosomotropic autophagy inhibitor chloroquine (CQ) 
rapidly killed tumor cells incubated in the absence of serum. CQ-induced lysosomal destabilization 
triggered: oxidative stress, mitochondrial depolarization, and mixed apoptosis/necrosis of serum-deprived 
cells. In the second study, lysosomal detergent N-dodecylimidazole (NDI) synergized in antitumor activity 
with the glycolytic inhibitor 2-deoxy-D-glucose (2DG). NDI-triggered release of lysosomal enzymes into the 
cytoplasm caused mitochondrial damage and blocked oxidative phosphorylation, which synergized with 
2DG-mediated glycolysis block in ATP reduction, oxidative stress, and necrosis. Interestingly, although both 
serum deprivation and 2DG stimulated autophagy, CQ- and NDI-induced autophagy suppression was 
irrelevant for their cytotoxicity. Importantly, CQ+food restriction and 2DG+NDI reduced melanoma growth 
in vivo. Conclusion: Autophagy independent antitumor effects of combined energy metabolism suppression 
and lysosomal destabilization might be exploited in cancer therapy.
PB  - Beograd : Srpsko društvo istraživača raka
C3  - 5th Congress of the Serbian Association for Cancer Research – SDIR-5 with international participation „Translational potential of cancer research in Serbia“
T1  - Dual targeting of energy metabolism and lysosomes as an anticancer strategy; It is not all about autophagy
SP  - 8
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_4709
ER  - 

@conference{
author = "Harhaji-Trajković, Ljubica and Kosić, Milica and Paunović, Verica and Ristić, Biljana and Bošnjak, Mihajlo and Zogović, Nevena and Mandić, Miloš and Tovilović-Kovačević, Gordana and Janjetović, Kristina and Trajković, Vladimir",
year = "2021",
abstract = "Background: Intensive proliferation of tumor cells consumes a lot of energy. In nutrient deficiency 
substrates for energy metabolism are obtained by lysosomal degradation of unnecessary/dysfunctional 
intracellular organelles/molecules in the process of autophagy. Leakage of enlarged unstable lysosomes, 
which characterize tumor cells, causes cell death. We investigated antitumor effect of combined targeting 
of lysosomes/autophagy and energy metabolism. Material and Methods: Toxicity against U251 human 
glioma and B16 mouse melanoma cells was measured by viability tests. Type/mechanisms of cell death 
were determined by flow cytometry, immunoblot, fluorescent/electron microscopy and confirmed by 
appropriate genetic/pharmacological inhibitors. Therapeutic potential was estimated in B16 melanoma bearing C57Bl/6 mice. Results: In the first study, lysosomotropic autophagy inhibitor chloroquine (CQ) 
rapidly killed tumor cells incubated in the absence of serum. CQ-induced lysosomal destabilization 
triggered: oxidative stress, mitochondrial depolarization, and mixed apoptosis/necrosis of serum-deprived 
cells. In the second study, lysosomal detergent N-dodecylimidazole (NDI) synergized in antitumor activity 
with the glycolytic inhibitor 2-deoxy-D-glucose (2DG). NDI-triggered release of lysosomal enzymes into the 
cytoplasm caused mitochondrial damage and blocked oxidative phosphorylation, which synergized with 
2DG-mediated glycolysis block in ATP reduction, oxidative stress, and necrosis. Interestingly, although both 
serum deprivation and 2DG stimulated autophagy, CQ- and NDI-induced autophagy suppression was 
irrelevant for their cytotoxicity. Importantly, CQ+food restriction and 2DG+NDI reduced melanoma growth 
in vivo. Conclusion: Autophagy independent antitumor effects of combined energy metabolism suppression 
and lysosomal destabilization might be exploited in cancer therapy.",
publisher = "Beograd : Srpsko društvo istraživača raka",
journal = "5th Congress of the Serbian Association for Cancer Research – SDIR-5 with international participation „Translational potential of cancer research in Serbia“",
title = "Dual targeting of energy metabolism and lysosomes as an anticancer strategy; It is not all about autophagy",
pages = "8",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_4709"
}

Harhaji-Trajković, L., Kosić, M., Paunović, V., Ristić, B., Bošnjak, M., Zogović, N., Mandić, M., Tovilović-Kovačević, G., Janjetović, K.,& Trajković, V.. (2021). Dual targeting of energy metabolism and lysosomes as an anticancer strategy; It is not all about autophagy. in 5th Congress of the Serbian Association for Cancer Research – SDIR-5 with international participation „Translational potential of cancer research in Serbia“
Beograd : Srpsko društvo istraživača raka., 8.
https://hdl.handle.net/21.15107/rcub_ibiss_4709

Harhaji-Trajković L, Kosić M, Paunović V, Ristić B, Bošnjak M, Zogović N, Mandić M, Tovilović-Kovačević G, Janjetović K, Trajković V. Dual targeting of energy metabolism and lysosomes as an anticancer strategy; It is not all about autophagy. in 5th Congress of the Serbian Association for Cancer Research – SDIR-5 with international participation „Translational potential of cancer research in Serbia“. 2021;:8.
https://hdl.handle.net/21.15107/rcub_ibiss_4709 .

Harhaji-Trajković, Ljubica, Kosić, Milica, Paunović, Verica, Ristić, Biljana, Bošnjak, Mihajlo, Zogović, Nevena, Mandić, Miloš, Tovilović-Kovačević, Gordana, Janjetović, Kristina, Trajković, Vladimir, "Dual targeting of energy metabolism and lysosomes as an anticancer strategy; It is not all about autophagy" in 5th Congress of the Serbian Association for Cancer Research – SDIR-5 with international participation „Translational potential of cancer research in Serbia“ (2021):8,
https://hdl.handle.net/21.15107/rcub_ibiss_4709 .

TY  - CONF
AU  - Stevanović, Danijela
AU  - Vučićević, Ljubica
AU  - Misirkić Marjanović, Maja
AU  - Paunović, Verica
AU  - Kosić, Milica
AU  - Mandić, Miloš
AU  - Ristić, Biljana
AU  - Bošnjak, Mihajlo
AU  - Janjetović, Kristina
AU  - Zogović, Nevena
AU  - Tovilović-Kovačević, Gordana
AU  - Harhaji-Trajković, Ljubica
AU  - Trajković, Vladimir
PY  - 2021
UR  - https://www.sfrre2021belgrade.rs/
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/4725
AB  - 6-hydroxydopamine (6-OHDA) and 1-methyl-4-phenylpyridinium (MPP+) are the most common neurotoxins used to induce experimental model of Parkinson’s disease both in vivo and in vitro. Neurotoxic action of 6-OHDA and MPP+
 is mediated by oxidative stress, mitochondrial damage and induction of apoptotic cell death. Natural disaccharide trehalose exhibits antioxidative properties and stimulates removal of damaged proteins, and thus exhibits powerful
neuroprotective effect in certain brain injury models. We investigated the effects of trehalose in 6-OHDA and MPP+
 - induced oxidative stress and neurotoxicity in human neuroblastoma SH-SY5Y cells. The effects of trehalose on the cell viability and death were assessed by MTT, crystal violet, lactate dehydrogenase assay and AnnexinV-FITC/propidium iodide staining. The production of reactive oxygen species was analyzed by flow cytometry using redox-sensitive dyes dihydrorhodamine 123 (DHR) and MitoSOX Red. Further, activation of stress-related MAP kinases, p38 and JNK were investigated by immunoblot analysis. Our study demonstrated that trehalose pretreatment significantly improved cell viability and reduced neurotoxic effect of 6-OHDA, while slightly decreased cell viability and increased neurotoxic effect of MPP+. Trehalose decreased the number of 6-OHDA-induced apoptotic cells (shown by the reduced % of Annexin V+ and AnnexinV+ PI+ cells) whereas it increased apoptosis in MPP+ treated cells. Flow
cytometric analysis of DHR and MitoSOX stained cells demonstrated that trehalose pretreatment significantly reduced 6-OHDA-triggered ROS and superoxide anion radical generation. However, in MPP+-treated neurons trehalose augmented oxidative stress and production of superoxide anion. Immunoblot analysis showed that trehalose significantly decreased p38 and JNK activation only in 6-OHDA treated cells. These results indicate that trehalose has different effects on oxidative stress induced by two different neurotoxins, 6-OHDA and MPP+, and suggests further
exploration of the mechanism of its antioxidative action.
PB  - Elsevier Inc.
C3  - Free Radical Research Europe (SFRR-E) Annual Meeting Abstracts “Redox biology in the 21st century: a new scientific discipline” 15-18 June 2021, Belgrade, Serbia
T1  - The opposite effects of trehalose on 6-hydroxydopamine and 1-methyl-4- phenylpyridinium induced oxidative stress in human neuroblastoma SH-SY5Y cells
DO  - 10.1016/j.freeradbiomed.2021.08.097
SP  - 94
ER  - 

@conference{
author = "Stevanović, Danijela and Vučićević, Ljubica and Misirkić Marjanović, Maja and Paunović, Verica and Kosić, Milica and Mandić, Miloš and Ristić, Biljana and Bošnjak, Mihajlo and Janjetović, Kristina and Zogović, Nevena and Tovilović-Kovačević, Gordana and Harhaji-Trajković, Ljubica and Trajković, Vladimir",
year = "2021",
abstract = "6-hydroxydopamine (6-OHDA) and 1-methyl-4-phenylpyridinium (MPP+) are the most common neurotoxins used to induce experimental model of Parkinson’s disease both in vivo and in vitro. Neurotoxic action of 6-OHDA and MPP+
 is mediated by oxidative stress, mitochondrial damage and induction of apoptotic cell death. Natural disaccharide trehalose exhibits antioxidative properties and stimulates removal of damaged proteins, and thus exhibits powerful
neuroprotective effect in certain brain injury models. We investigated the effects of trehalose in 6-OHDA and MPP+
 - induced oxidative stress and neurotoxicity in human neuroblastoma SH-SY5Y cells. The effects of trehalose on the cell viability and death were assessed by MTT, crystal violet, lactate dehydrogenase assay and AnnexinV-FITC/propidium iodide staining. The production of reactive oxygen species was analyzed by flow cytometry using redox-sensitive dyes dihydrorhodamine 123 (DHR) and MitoSOX Red. Further, activation of stress-related MAP kinases, p38 and JNK were investigated by immunoblot analysis. Our study demonstrated that trehalose pretreatment significantly improved cell viability and reduced neurotoxic effect of 6-OHDA, while slightly decreased cell viability and increased neurotoxic effect of MPP+. Trehalose decreased the number of 6-OHDA-induced apoptotic cells (shown by the reduced % of Annexin V+ and AnnexinV+ PI+ cells) whereas it increased apoptosis in MPP+ treated cells. Flow
cytometric analysis of DHR and MitoSOX stained cells demonstrated that trehalose pretreatment significantly reduced 6-OHDA-triggered ROS and superoxide anion radical generation. However, in MPP+-treated neurons trehalose augmented oxidative stress and production of superoxide anion. Immunoblot analysis showed that trehalose significantly decreased p38 and JNK activation only in 6-OHDA treated cells. These results indicate that trehalose has different effects on oxidative stress induced by two different neurotoxins, 6-OHDA and MPP+, and suggests further
exploration of the mechanism of its antioxidative action.",
publisher = "Elsevier Inc.",
journal = "Free Radical Research Europe (SFRR-E) Annual Meeting Abstracts “Redox biology in the 21st century: a new scientific discipline” 15-18 June 2021, Belgrade, Serbia",
title = "The opposite effects of trehalose on 6-hydroxydopamine and 1-methyl-4- phenylpyridinium induced oxidative stress in human neuroblastoma SH-SY5Y cells",
doi = "10.1016/j.freeradbiomed.2021.08.097",
pages = "94"
}

Stevanović, D., Vučićević, L., Misirkić Marjanović, M., Paunović, V., Kosić, M., Mandić, M., Ristić, B., Bošnjak, M., Janjetović, K., Zogović, N., Tovilović-Kovačević, G., Harhaji-Trajković, L.,& Trajković, V.. (2021). The opposite effects of trehalose on 6-hydroxydopamine and 1-methyl-4- phenylpyridinium induced oxidative stress in human neuroblastoma SH-SY5Y cells. in Free Radical Research Europe (SFRR-E) Annual Meeting Abstracts “Redox biology in the 21st century: a new scientific discipline” 15-18 June 2021, Belgrade, Serbia
Elsevier Inc.., 94.
https://doi.org/10.1016/j.freeradbiomed.2021.08.097

Stevanović D, Vučićević L, Misirkić Marjanović M, Paunović V, Kosić M, Mandić M, Ristić B, Bošnjak M, Janjetović K, Zogović N, Tovilović-Kovačević G, Harhaji-Trajković L, Trajković V. The opposite effects of trehalose on 6-hydroxydopamine and 1-methyl-4- phenylpyridinium induced oxidative stress in human neuroblastoma SH-SY5Y cells. in Free Radical Research Europe (SFRR-E) Annual Meeting Abstracts “Redox biology in the 21st century: a new scientific discipline” 15-18 June 2021, Belgrade, Serbia. 2021;:94.
doi:10.1016/j.freeradbiomed.2021.08.097 .

Stevanović, Danijela, Vučićević, Ljubica, Misirkić Marjanović, Maja, Paunović, Verica, Kosić, Milica, Mandić, Miloš, Ristić, Biljana, Bošnjak, Mihajlo, Janjetović, Kristina, Zogović, Nevena, Tovilović-Kovačević, Gordana, Harhaji-Trajković, Ljubica, Trajković, Vladimir, "The opposite effects of trehalose on 6-hydroxydopamine and 1-methyl-4- phenylpyridinium induced oxidative stress in human neuroblastoma SH-SY5Y cells" in Free Radical Research Europe (SFRR-E) Annual Meeting Abstracts “Redox biology in the 21st century: a new scientific discipline” 15-18 June 2021, Belgrade, Serbia (2021):94,
https://doi.org/10.1016/j.freeradbiomed.2021.08.097 . .

TY  - JOUR
AU  - Misirkić Marjanović, Maja
AU  - Vučićević, Ljubica
AU  - Despotović, Ana
AU  - Stamenković, Marina
AU  - Janjetović, Kristina
PY  - 2021
UR  - http://www.ajcr.us/files/ajcr0136757.pdf
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/4679
AB  - Metformin has been known to treat type 2 diabetes for decades and is widely prescribed antidiabetic drug.
Recently, its anticancer potential has also been discovered. Moreover, metformin has low cost thus it has attained profound research interest. Comprehensing the complexity of the molecular regulatory networks in cancer provides a mode for advancement of research in cancer development and treatment. Metformin targets many pathways that play an important role in cancer cell survival outcome. Here, we described anticancer activity of metformin on the AMPK dependent/independent mechanisms regulating metabolism, oncogene/tumor suppressor signaling pathways together with the issue of clinical studies. We also provided brief overwiev about recently described metformin’s role in cancer immunity. Insight in these complex molecular networks, will simplify application of metformin in clinical trials and contribute to improvement of anti-cancer therapy.
PB  - Madison, USA : e-Century Publishing Corporation
T2  - American Journal of Cancer Research
T1  - Dual anticancer role of metformin: an old drug regulating AMPK dependent/independent pathways in metabolic, oncogenic/tumorsuppresing and immunity context
IS  - 11
VL  - 11
SP  - 5625
EP  - 5643
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_4679
ER  - 

@article{
author = "Misirkić Marjanović, Maja and Vučićević, Ljubica and Despotović, Ana and Stamenković, Marina and Janjetović, Kristina",
year = "2021",
abstract = "Metformin has been known to treat type 2 diabetes for decades and is widely prescribed antidiabetic drug.
Recently, its anticancer potential has also been discovered. Moreover, metformin has low cost thus it has attained profound research interest. Comprehensing the complexity of the molecular regulatory networks in cancer provides a mode for advancement of research in cancer development and treatment. Metformin targets many pathways that play an important role in cancer cell survival outcome. Here, we described anticancer activity of metformin on the AMPK dependent/independent mechanisms regulating metabolism, oncogene/tumor suppressor signaling pathways together with the issue of clinical studies. We also provided brief overwiev about recently described metformin’s role in cancer immunity. Insight in these complex molecular networks, will simplify application of metformin in clinical trials and contribute to improvement of anti-cancer therapy.",
publisher = "Madison, USA : e-Century Publishing Corporation",
journal = "American Journal of Cancer Research",
title = "Dual anticancer role of metformin: an old drug regulating AMPK dependent/independent pathways in metabolic, oncogenic/tumorsuppresing and immunity context",
number = "11",
volume = "11",
pages = "5625-5643",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_4679"
}

Misirkić Marjanović, M., Vučićević, L., Despotović, A., Stamenković, M.,& Janjetović, K.. (2021). Dual anticancer role of metformin: an old drug regulating AMPK dependent/independent pathways in metabolic, oncogenic/tumorsuppresing and immunity context. in American Journal of Cancer Research
Madison, USA : e-Century Publishing Corporation., 11(11), 5625-5643.
https://hdl.handle.net/21.15107/rcub_ibiss_4679

Misirkić Marjanović M, Vučićević L, Despotović A, Stamenković M, Janjetović K. Dual anticancer role of metformin: an old drug regulating AMPK dependent/independent pathways in metabolic, oncogenic/tumorsuppresing and immunity context. in American Journal of Cancer Research. 2021;11(11):5625-5643.
https://hdl.handle.net/21.15107/rcub_ibiss_4679 .

Misirkić Marjanović, Maja, Vučićević, Ljubica, Despotović, Ana, Stamenković, Marina, Janjetović, Kristina, "Dual anticancer role of metformin: an old drug regulating AMPK dependent/independent pathways in metabolic, oncogenic/tumorsuppresing and immunity context" in American Journal of Cancer Research, 11, no. 11 (2021):5625-5643,
https://hdl.handle.net/21.15107/rcub_ibiss_4679 .

TY  - JOUR
AU  - Stamenković, Marina
AU  - Janjetović, Kristina
AU  - Paunović, Verica
AU  - Ćirić, Darko
AU  - Kravić-Stevović, Tamara
AU  - Trajković, Vladimir
PY  - 2019
UR  - https://www.sciencedirect.com/science/article/pii/S0014299919304923?via%3Dihub
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3448
AB  - We performed a comparative analysis of molecular cytotoxic mechanisms of lysosomal autophagy inhibitors bafilomycin A1, chloroquine, and ammonium chloride in B16 mouse melanoma cells. All agents caused oxidative stress, mitochondrial depolarization, and caspase-dependent apoptotic death, which was not affected by genetic inactivation of autophagy. Cathepsin inhibition reduced only the cytotoxicity of chloroquine, indicating its ability to cause lysosomal membrane permeabilization. Bafilomycin reduced the mRNA levels of anti-apoptotic Bcl-2, while chloroquine and ammonium chloride increased the mRNA expression of pro-apoptotic Pten and Puma, as well as anti-apoptotic Bcl-xL. Ammonium chloride additionally increased the mRNA expression of pro-apoptotic Bim and p53. All three agents decreased the activity of mechanistic target of rapamycin (mTOR) and increased the activation of p38 mitogen-activated protein kinase (MAPK). Chloroquine and ammonium chloride additionally stimulated the phosphorylation of extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK), respectively, while only bafilomycin increased the phosphorylation of the energy sensor AMP-activated protein kinase (AMPK). mTOR activator leucine did not affect the cytotoxicity of lysosomal inhibitors. p38 MAPK inhibitor SB203580 reduced the cytotoxicity of bafilomycin but increased that of chloroquine and ammonium chloride. The pharmacological inhibition of ERK1/2, JNK, and AMPK potentiated the cytotoxicity of chloroquine, ammonium chloride, and bafilomycin, respectively. The observed mechanistic differences were associated with antagonistic interactions of lysosomal inhibitors in B16 cell killing. In conclusion, all investigated lysosomal inhibitors cause autophagy-independent mitochondrial dysfunction and apoptotic death, but differ in the ability to affect lysosomal permeabilization, balance between pro- and anti-apoptotic molecules of Bcl-2 family, and MAPK/AMPK signaling.
T2  - European Journal of Pharmacology
T1  - Comparative analysis of cell death mechanisms induced by lysosomal autophagy inhibitors.
VL  - 859
DO  - 10.1016/j.ejphar.2019.172540
SP  - 172540
ER  - 

@article{
author = "Stamenković, Marina and Janjetović, Kristina and Paunović, Verica and Ćirić, Darko and Kravić-Stevović, Tamara and Trajković, Vladimir",
year = "2019",
abstract = "We performed a comparative analysis of molecular cytotoxic mechanisms of lysosomal autophagy inhibitors bafilomycin A1, chloroquine, and ammonium chloride in B16 mouse melanoma cells. All agents caused oxidative stress, mitochondrial depolarization, and caspase-dependent apoptotic death, which was not affected by genetic inactivation of autophagy. Cathepsin inhibition reduced only the cytotoxicity of chloroquine, indicating its ability to cause lysosomal membrane permeabilization. Bafilomycin reduced the mRNA levels of anti-apoptotic Bcl-2, while chloroquine and ammonium chloride increased the mRNA expression of pro-apoptotic Pten and Puma, as well as anti-apoptotic Bcl-xL. Ammonium chloride additionally increased the mRNA expression of pro-apoptotic Bim and p53. All three agents decreased the activity of mechanistic target of rapamycin (mTOR) and increased the activation of p38 mitogen-activated protein kinase (MAPK). Chloroquine and ammonium chloride additionally stimulated the phosphorylation of extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK), respectively, while only bafilomycin increased the phosphorylation of the energy sensor AMP-activated protein kinase (AMPK). mTOR activator leucine did not affect the cytotoxicity of lysosomal inhibitors. p38 MAPK inhibitor SB203580 reduced the cytotoxicity of bafilomycin but increased that of chloroquine and ammonium chloride. The pharmacological inhibition of ERK1/2, JNK, and AMPK potentiated the cytotoxicity of chloroquine, ammonium chloride, and bafilomycin, respectively. The observed mechanistic differences were associated with antagonistic interactions of lysosomal inhibitors in B16 cell killing. In conclusion, all investigated lysosomal inhibitors cause autophagy-independent mitochondrial dysfunction and apoptotic death, but differ in the ability to affect lysosomal permeabilization, balance between pro- and anti-apoptotic molecules of Bcl-2 family, and MAPK/AMPK signaling.",
journal = "European Journal of Pharmacology",
title = "Comparative analysis of cell death mechanisms induced by lysosomal autophagy inhibitors.",
volume = "859",
doi = "10.1016/j.ejphar.2019.172540",
pages = "172540"
}

Stamenković, M., Janjetović, K., Paunović, V., Ćirić, D., Kravić-Stevović, T.,& Trajković, V.. (2019). Comparative analysis of cell death mechanisms induced by lysosomal autophagy inhibitors.. in European Journal of Pharmacology, 859, 172540.
https://doi.org/10.1016/j.ejphar.2019.172540

Stamenković M, Janjetović K, Paunović V, Ćirić D, Kravić-Stevović T, Trajković V. Comparative analysis of cell death mechanisms induced by lysosomal autophagy inhibitors.. in European Journal of Pharmacology. 2019;859:172540.
doi:10.1016/j.ejphar.2019.172540 .

Stamenković, Marina, Janjetović, Kristina, Paunović, Verica, Ćirić, Darko, Kravić-Stevović, Tamara, Trajković, Vladimir, "Comparative analysis of cell death mechanisms induced by lysosomal autophagy inhibitors." in European Journal of Pharmacology, 859 (2019):172540,
https://doi.org/10.1016/j.ejphar.2019.172540 . .

TY  - JOUR
AU  - Paunović, Verica
AU  - Vukovič Petrović, Irena
AU  - Milenković, Marina
AU  - Janjetović, Kristina
AU  - Pravica, Vera
AU  - Dujmović, Irena
AU  - Milošević, Emina
AU  - Martinović, Vanja
AU  - Mesaroš, Šarlota
AU  - Drulović, Jelena
AU  - Trajković, Vladimir
PY  - 2018
UR  - http://www.jni-journal.com/article/S0165-5728(17)30538-6/abstract
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3014
AB  - Autophagy, a process of controlled self-digestion which regulates cell homeostasis, is involved in innate and adaptive immunity. We investigated the expression of autophagy genes and autophagic activity in distinct lymphocyte populations in treatment-naive MS patients. The mRNA and protein levels of autophagy-related (ATG)5, required for autophagosome formation, were increased in CD4+and CD4-T cells, but not B cells of MS patients compared to control subjects. The expression of other investigated autophagy genes, as well as the autophagic activity, did not significantly differ between the two groups. ATG5 mRNA levels in CD4+T cells from MS patients were positively correlated with those of the proinflammatory cytokine tumor necrosis factor. These data suggest that autophagy-independent increase in ATG5 expression might be associated with the proinflammatory capacity of T cells in multiple sclerosis.
T2  - Journal of Neuroimmunology
T1  - Autophagy-independent increase of ATG5 expression in T cells of multiple sclerosis patients.
VL  - 319
DO  - 10.1016/j.jneuroim.2018.03.001
SP  - 100
EP  - 105
ER  - 

@article{
author = "Paunović, Verica and Vukovič Petrović, Irena and Milenković, Marina and Janjetović, Kristina and Pravica, Vera and Dujmović, Irena and Milošević, Emina and Martinović, Vanja and Mesaroš, Šarlota and Drulović, Jelena and Trajković, Vladimir",
year = "2018",
abstract = "Autophagy, a process of controlled self-digestion which regulates cell homeostasis, is involved in innate and adaptive immunity. We investigated the expression of autophagy genes and autophagic activity in distinct lymphocyte populations in treatment-naive MS patients. The mRNA and protein levels of autophagy-related (ATG)5, required for autophagosome formation, were increased in CD4+and CD4-T cells, but not B cells of MS patients compared to control subjects. The expression of other investigated autophagy genes, as well as the autophagic activity, did not significantly differ between the two groups. ATG5 mRNA levels in CD4+T cells from MS patients were positively correlated with those of the proinflammatory cytokine tumor necrosis factor. These data suggest that autophagy-independent increase in ATG5 expression might be associated with the proinflammatory capacity of T cells in multiple sclerosis.",
journal = "Journal of Neuroimmunology",
title = "Autophagy-independent increase of ATG5 expression in T cells of multiple sclerosis patients.",
volume = "319",
doi = "10.1016/j.jneuroim.2018.03.001",
pages = "100-105"
}

Paunović, V., Vukovič Petrović, I., Milenković, M., Janjetović, K., Pravica, V., Dujmović, I., Milošević, E., Martinović, V., Mesaroš, Š., Drulović, J.,& Trajković, V.. (2018). Autophagy-independent increase of ATG5 expression in T cells of multiple sclerosis patients.. in Journal of Neuroimmunology, 319, 100-105.
https://doi.org/10.1016/j.jneuroim.2018.03.001

Paunović V, Vukovič Petrović I, Milenković M, Janjetović K, Pravica V, Dujmović I, Milošević E, Martinović V, Mesaroš Š, Drulović J, Trajković V. Autophagy-independent increase of ATG5 expression in T cells of multiple sclerosis patients.. in Journal of Neuroimmunology. 2018;319:100-105.
doi:10.1016/j.jneuroim.2018.03.001 .

Paunović, Verica, Vukovič Petrović, Irena, Milenković, Marina, Janjetović, Kristina, Pravica, Vera, Dujmović, Irena, Milošević, Emina, Martinović, Vanja, Mesaroš, Šarlota, Drulović, Jelena, Trajković, Vladimir, "Autophagy-independent increase of ATG5 expression in T cells of multiple sclerosis patients." in Journal of Neuroimmunology, 319 (2018):100-105,
https://doi.org/10.1016/j.jneuroim.2018.03.001 . .

TY  - JOUR
AU  - Šumarac-Dumanović, Mirjana
AU  - Apostolović, Milica
AU  - Janjetović, Kristina
AU  - Jeremić, Danka
AU  - Popadić, Dušan
AU  - Ljubić, Aleksandar
AU  - Micić, Jelena
AU  - Dukanac-Stamenković, Jelena
AU  - Tubić, Aleksandra
AU  - Stevanović, Darko
AU  - Micić, Dragan
AU  - Trajković, Vladimir
PY  - 2017
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6352
AB  - Autophagy, a process of controlled cellular self-digestion, could be involved in cyclic remodeling
of the human endometrium. We investigated endometrial mRNA expression of 23 autophagyrelated
(ATG) genes and transcription factors in healthy controls (n = 12) and anovulatory
polycystic ovary syndrome (PCOS) patients (n = 24), as well as in their subgroup (n = 12) before
and after metformin treatment. The mRNA levels of transcription factor forkhead box protein O1
(FOXO1) and several molecules involved in autophagosome formation (ATG13, RB1-inducible
coiled-coil 1), autophagosome nucleation (ATG14, beclin 1, SH3-domain GRB2-like endophilin
B1), autophagosome elongation (ATG3, ATG5, g-aminobutyric acid receptor-associated protein -
GABARAP), and delivery of ubiquitinated proteins to autophagosomes (sequestosome 1), were
significantly reduced in anovulatory PCOS compared to healthy endometrium. Free androgen
index, but not free estrogen index, insulin levels, or BMI, negatively correlated with the
endometrial expression of ATG3, ATG14, and GABARAP in PCOS patients. Treatment of
PCOS patients with metformin (2 g/day for 3 months) significantly increased the endometrial
mRNA levels of FOXO1, ATG3, and UV radiation resistance-associated gene. These data
suggest that increased androgen availability in PCOS is associated with metformin-sensitive
transcriptional downregulation of endometrial autophagy
PB  - Elsevier
T2  - Molecular and Cellular Endocrinology
T1  - Downregulation of autophagy gene expression in endometria from women with polycystic ovary syndrome
VL  - 440
DO  - 10.1016/j.mce.2016.11.009
SP  - 116
EP  - 124
ER  - 

@article{
author = "Šumarac-Dumanović, Mirjana and Apostolović, Milica and Janjetović, Kristina and Jeremić, Danka and Popadić, Dušan and Ljubić, Aleksandar and Micić, Jelena and Dukanac-Stamenković, Jelena and Tubić, Aleksandra and Stevanović, Darko and Micić, Dragan and Trajković, Vladimir",
year = "2017",
abstract = "Autophagy, a process of controlled cellular self-digestion, could be involved in cyclic remodeling
of the human endometrium. We investigated endometrial mRNA expression of 23 autophagyrelated
(ATG) genes and transcription factors in healthy controls (n = 12) and anovulatory
polycystic ovary syndrome (PCOS) patients (n = 24), as well as in their subgroup (n = 12) before
and after metformin treatment. The mRNA levels of transcription factor forkhead box protein O1
(FOXO1) and several molecules involved in autophagosome formation (ATG13, RB1-inducible
coiled-coil 1), autophagosome nucleation (ATG14, beclin 1, SH3-domain GRB2-like endophilin
B1), autophagosome elongation (ATG3, ATG5, g-aminobutyric acid receptor-associated protein -
GABARAP), and delivery of ubiquitinated proteins to autophagosomes (sequestosome 1), were
significantly reduced in anovulatory PCOS compared to healthy endometrium. Free androgen
index, but not free estrogen index, insulin levels, or BMI, negatively correlated with the
endometrial expression of ATG3, ATG14, and GABARAP in PCOS patients. Treatment of
PCOS patients with metformin (2 g/day for 3 months) significantly increased the endometrial
mRNA levels of FOXO1, ATG3, and UV radiation resistance-associated gene. These data
suggest that increased androgen availability in PCOS is associated with metformin-sensitive
transcriptional downregulation of endometrial autophagy",
publisher = "Elsevier",
journal = "Molecular and Cellular Endocrinology",
title = "Downregulation of autophagy gene expression in endometria from women with polycystic ovary syndrome",
volume = "440",
doi = "10.1016/j.mce.2016.11.009",
pages = "116-124"
}

Šumarac-Dumanović, M., Apostolović, M., Janjetović, K., Jeremić, D., Popadić, D., Ljubić, A., Micić, J., Dukanac-Stamenković, J., Tubić, A., Stevanović, D., Micić, D.,& Trajković, V.. (2017). Downregulation of autophagy gene expression in endometria from women with polycystic ovary syndrome. in Molecular and Cellular Endocrinology
Elsevier., 440, 116-124.
https://doi.org/10.1016/j.mce.2016.11.009

Šumarac-Dumanović M, Apostolović M, Janjetović K, Jeremić D, Popadić D, Ljubić A, Micić J, Dukanac-Stamenković J, Tubić A, Stevanović D, Micić D, Trajković V. Downregulation of autophagy gene expression in endometria from women with polycystic ovary syndrome. in Molecular and Cellular Endocrinology. 2017;440:116-124.
doi:10.1016/j.mce.2016.11.009 .

Šumarac-Dumanović, Mirjana, Apostolović, Milica, Janjetović, Kristina, Jeremić, Danka, Popadić, Dušan, Ljubić, Aleksandar, Micić, Jelena, Dukanac-Stamenković, Jelena, Tubić, Aleksandra, Stevanović, Darko, Micić, Dragan, Trajković, Vladimir, "Downregulation of autophagy gene expression in endometria from women with polycystic ovary syndrome" in Molecular and Cellular Endocrinology, 440 (2017):116-124,
https://doi.org/10.1016/j.mce.2016.11.009 . .

TY  - JOUR
AU  - Zogović, Nevena
AU  - Tovilović-Kovačević, Gordana
AU  - Misirkić Marjanović, Maja
AU  - Vučićević, Ljubica
AU  - Janjetović, Kristina
AU  - Harhaji-Trajković, Ljubica
AU  - Trajkovic, Vladimir
PY  - 2015
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/1978
AB  - We explored the interplay between the intracellular energy sensor
   AMP-activated protein kinase (AMPK), extracellular signal-regulated
   kinase (ERK), and autophagy in phorbol myristate acetate (PMA)-induced
   neuronal differentiation of SH-SY5Y human neuroblastoma cells.
   PMA-triggered expression of neuronal markers (dopamine transporter,
   microtubule-associated protein 2, -tubulin) was associated with an
   autophagic response, measured by the conversion of
   microtubule-associated protein light chain 3 (LC3)-I to
   autophagosome-bound LC3-II, increase in autophagic flux, and expression
   of autophagy-related (Atg) proteins Atg7 and beclin-1. This coincided
   with the transient activation of AMPK and sustained activation of ERK.
   Pharmacological inhibition or RNA interference-mediated silencing of
   AMPK suppressed PMA-induced expression of neuronal markers, as well as
   ERK activation and autophagy. A selective pharmacological blockade of
   ERK prevented PMA-induced neuronal differentiation and autophagy
   induction without affecting AMPK phosphorylation. Conversely, the
   inhibition of autophagy downstream of AMPK/ERK, either by
   pharmacological agents or LC3 knockdown, promoted the expression of
   neuronal markers, thus indicating a role of autophagy in the suppression
   of PMA-induced differentiation of SH-SY5Y cells. Therefore, PMA-induced
   neuronal differentiation of SH-SY5Y cells depends on a complex interplay
   between AMPK, ERK, and autophagy, in which the stimulatory effects of
   AMPK/ERK signaling are counteracted by the coinciding autophagic
   response.
T2  - Journal of Neurochemistry
T1  - Coordinated activation of AMP-activated protein kinase, extracellular
 signal-regulated kinase, and autophagy regulates phorbol myristate
 acetate-induced differentiation of SH-SY5Y neuroblastoma cells
IS  - 2
VL  - 133
DO  - 10.1111/jnc.12980
SP  - 223
EP  - 232
ER  - 

@article{
author = "Zogović, Nevena and Tovilović-Kovačević, Gordana and Misirkić Marjanović, Maja and Vučićević, Ljubica and Janjetović, Kristina and Harhaji-Trajković, Ljubica and Trajkovic, Vladimir",
year = "2015",
abstract = "We explored the interplay between the intracellular energy sensor
   AMP-activated protein kinase (AMPK), extracellular signal-regulated
   kinase (ERK), and autophagy in phorbol myristate acetate (PMA)-induced
   neuronal differentiation of SH-SY5Y human neuroblastoma cells.
   PMA-triggered expression of neuronal markers (dopamine transporter,
   microtubule-associated protein 2, -tubulin) was associated with an
   autophagic response, measured by the conversion of
   microtubule-associated protein light chain 3 (LC3)-I to
   autophagosome-bound LC3-II, increase in autophagic flux, and expression
   of autophagy-related (Atg) proteins Atg7 and beclin-1. This coincided
   with the transient activation of AMPK and sustained activation of ERK.
   Pharmacological inhibition or RNA interference-mediated silencing of
   AMPK suppressed PMA-induced expression of neuronal markers, as well as
   ERK activation and autophagy. A selective pharmacological blockade of
   ERK prevented PMA-induced neuronal differentiation and autophagy
   induction without affecting AMPK phosphorylation. Conversely, the
   inhibition of autophagy downstream of AMPK/ERK, either by
   pharmacological agents or LC3 knockdown, promoted the expression of
   neuronal markers, thus indicating a role of autophagy in the suppression
   of PMA-induced differentiation of SH-SY5Y cells. Therefore, PMA-induced
   neuronal differentiation of SH-SY5Y cells depends on a complex interplay
   between AMPK, ERK, and autophagy, in which the stimulatory effects of
   AMPK/ERK signaling are counteracted by the coinciding autophagic
   response.",
journal = "Journal of Neurochemistry",
title = "Coordinated activation of AMP-activated protein kinase, extracellular
 signal-regulated kinase, and autophagy regulates phorbol myristate
 acetate-induced differentiation of SH-SY5Y neuroblastoma cells",
number = "2",
volume = "133",
doi = "10.1111/jnc.12980",
pages = "223-232"
}

Zogović, N., Tovilović-Kovačević, G., Misirkić Marjanović, M., Vučićević, L., Janjetović, K., Harhaji-Trajković, L.,& Trajkovic, V.. (2015). Coordinated activation of AMP-activated protein kinase, extracellular
 signal-regulated kinase, and autophagy regulates phorbol myristate
 acetate-induced differentiation of SH-SY5Y neuroblastoma cells. in Journal of Neurochemistry, 133(2), 223-232.
https://doi.org/10.1111/jnc.12980

Zogović N, Tovilović-Kovačević G, Misirkić Marjanović M, Vučićević L, Janjetović K, Harhaji-Trajković L, Trajkovic V. Coordinated activation of AMP-activated protein kinase, extracellular
 signal-regulated kinase, and autophagy regulates phorbol myristate
 acetate-induced differentiation of SH-SY5Y neuroblastoma cells. in Journal of Neurochemistry. 2015;133(2):223-232.
doi:10.1111/jnc.12980 .

Zogović, Nevena, Tovilović-Kovačević, Gordana, Misirkić Marjanović, Maja, Vučićević, Ljubica, Janjetović, Kristina, Harhaji-Trajković, Ljubica, Trajkovic, Vladimir, "Coordinated activation of AMP-activated protein kinase, extracellular
 signal-regulated kinase, and autophagy regulates phorbol myristate
 acetate-induced differentiation of SH-SY5Y neuroblastoma cells" in Journal of Neurochemistry, 133, no. 2 (2015):223-232,
https://doi.org/10.1111/jnc.12980 . .

TY  - JOUR
AU  - Milovanovic, E. Sudar
AU  - Jovanovic, A.
AU  - Misirkic-Marjanovic, M.
AU  - Vučićević, Ljubica
AU  - Janjetović, Kristina
AU  - Isenovic, E. R.
PY  - 2015
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/2342
AB  - The aim of this study was to examine the effects of ghrelin on
   regulation of cardiac inducible nitric oxide synthase (iNOS)
   activity/expression in high fat (HF), obese rats.
   For this study, male Wistar rats fed with HF diet (30 \% fat) for 4
   weeks were injected every 24 h for 5 days intracerebroventriculary (ICV)
   with ghrelin (0.3 nmol/5 mu l) or with an equal volume of phosphate
   buffered saline (PBS). Control rats were ICV injected with an equal
   volume of PBS. Glucose, insulin and nitric oxide (NO) concentrations
   were measured in serum, while arginase activity and citrulline
   concentrations were measured in heart lysate. Protein iNOS and
   regulatory subunit of nuclear factor-kappa B (NF kappa B-p65),
   phosphorylation of enzymes protein kinase B (Akt) at Ser(473), and
   extracellular signal-regulated kinases 1/2 (ERK1/2) at Tyr(202)/Tyr(204)
   were determined in heart lysate by Western blot. For gene expression of
   iNOS qRT-PCR was used.
   Results show significantly (p < 0.01) higher serum NO production in
   ghrelin treated HF rats compared with HF rats. Ghrelin significantly
   reduced citrulline concentration (p < 0.05) and arginase activity (p <
   0.01) in HF rats. In ghrelin treated HF rats, gene and protein
   expression of iNOS and NF kappa B-p65 levels were significantly (p <
   0.05) increased compared with HF rats. Increased phosphorylation of Akt
   (p < 0.01) and decreased (p < 0.05) ERK1/2 phosphorylation were detected
   in HF ghrelin treated rats compared with HF rats hearts.
   Results from this study indicate that exogenous ghrelin induces
   expression and activity of cardiac iNOS via Akt phosphorylation followed
   by NF kappa B activation in HF rats.
T2  - Experimental and Clinical Endocrinology & Diabetes
T1  - Effects of Intracerebroventricularly (ICV) Injected Ghrelin on Cardiac
 Inducible Nitric Oxide Synthase Activity/Expression in Obese Rats
IS  - 10
VL  - 123
DO  - 10.1055/s-0035-1559758
SP  - 581
EP  - 588
ER  - 

@article{
author = "Milovanovic, E. Sudar and Jovanovic, A. and Misirkic-Marjanovic, M. and Vučićević, Ljubica and Janjetović, Kristina and Isenovic, E. R.",
year = "2015",
abstract = "The aim of this study was to examine the effects of ghrelin on
   regulation of cardiac inducible nitric oxide synthase (iNOS)
   activity/expression in high fat (HF), obese rats.
   For this study, male Wistar rats fed with HF diet (30 \% fat) for 4
   weeks were injected every 24 h for 5 days intracerebroventriculary (ICV)
   with ghrelin (0.3 nmol/5 mu l) or with an equal volume of phosphate
   buffered saline (PBS). Control rats were ICV injected with an equal
   volume of PBS. Glucose, insulin and nitric oxide (NO) concentrations
   were measured in serum, while arginase activity and citrulline
   concentrations were measured in heart lysate. Protein iNOS and
   regulatory subunit of nuclear factor-kappa B (NF kappa B-p65),
   phosphorylation of enzymes protein kinase B (Akt) at Ser(473), and
   extracellular signal-regulated kinases 1/2 (ERK1/2) at Tyr(202)/Tyr(204)
   were determined in heart lysate by Western blot. For gene expression of
   iNOS qRT-PCR was used.
   Results show significantly (p < 0.01) higher serum NO production in
   ghrelin treated HF rats compared with HF rats. Ghrelin significantly
   reduced citrulline concentration (p < 0.05) and arginase activity (p <
   0.01) in HF rats. In ghrelin treated HF rats, gene and protein
   expression of iNOS and NF kappa B-p65 levels were significantly (p <
   0.05) increased compared with HF rats. Increased phosphorylation of Akt
   (p < 0.01) and decreased (p < 0.05) ERK1/2 phosphorylation were detected
   in HF ghrelin treated rats compared with HF rats hearts.
   Results from this study indicate that exogenous ghrelin induces
   expression and activity of cardiac iNOS via Akt phosphorylation followed
   by NF kappa B activation in HF rats.",
journal = "Experimental and Clinical Endocrinology & Diabetes",
title = "Effects of Intracerebroventricularly (ICV) Injected Ghrelin on Cardiac
 Inducible Nitric Oxide Synthase Activity/Expression in Obese Rats",
number = "10",
volume = "123",
doi = "10.1055/s-0035-1559758",
pages = "581-588"
}

Milovanovic, E. S., Jovanovic, A., Misirkic-Marjanovic, M., Vučićević, L., Janjetović, K.,& Isenovic, E. R.. (2015). Effects of Intracerebroventricularly (ICV) Injected Ghrelin on Cardiac
 Inducible Nitric Oxide Synthase Activity/Expression in Obese Rats. in Experimental and Clinical Endocrinology & Diabetes, 123(10), 581-588.
https://doi.org/10.1055/s-0035-1559758

Milovanovic ES, Jovanovic A, Misirkic-Marjanovic M, Vučićević L, Janjetović K, Isenovic ER. Effects of Intracerebroventricularly (ICV) Injected Ghrelin on Cardiac
 Inducible Nitric Oxide Synthase Activity/Expression in Obese Rats. in Experimental and Clinical Endocrinology & Diabetes. 2015;123(10):581-588.
doi:10.1055/s-0035-1559758 .

Milovanovic, E. Sudar, Jovanovic, A., Misirkic-Marjanovic, M., Vučićević, Ljubica, Janjetović, Kristina, Isenovic, E. R., "Effects of Intracerebroventricularly (ICV) Injected Ghrelin on Cardiac
 Inducible Nitric Oxide Synthase Activity/Expression in Obese Rats" in Experimental and Clinical Endocrinology & Diabetes, 123, no. 10 (2015):581-588,
https://doi.org/10.1055/s-0035-1559758 . .

TY  - THES
AU  - Janjetović, Kristina
PY  - 2014
UR  - http://eteze.bg.ac.rs/application/showtheses?thesesId=2117
UR  - https://fedorabg.bg.ac.rs/fedora/get/o:9963/bdef:Content/download
UR  - http://vbs.rs/scripts/cobiss?command=DISPLAY&base=70036&RID=46947599
UR  - http://nardus.mpn.gov.rs/123456789/2460
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/2440
AB  - U ovoj disertaciji ispitivan je efekat antidijabetskog leka metformina na
apoptozu celijskih linija melanoma i glioma in vitro, u odsustvu i prisustvu
hemoterapeutika cisplatina. Takode smo bili zainteresovani za uticaj metformina na rast
melanoma in vivo.
U odsustvu cisplatina po prvi put je pokazan dvojan antiglioma efekat
metformina na celijskoj liniji glioma pacova C6. U celijskim kulturama glioma pacova
C6 male gustine metformin je zaustavio progresiju celijskog ciklusa u G0/G1 fazi, bez
znacajnog povecanja celijske smrti. Sa druge strane, u konfluentnim kulturama C6 celija
metformin je izazvao izuzetno povecanje apoptoze koja je zavisna od kaspaza,
depolarizacije mitohondrija, oksidativnog stresa i povezana sa aktivacijom JNK (engl.
c-Jun N-terminal kinase). Apoptoza indukovana metforminom je u potpunosti sprecena
supstancama koje blokiraju promenu propustljivosti membrane mitohondrija
(ciklosporin A) i produkciju reaktivnih kiseonicnih vrsta (N-acetilcistein), dok su je
inhibitori aktivacije JNK (SP600125) ili glikolize (natrijumfluorid, jodoacetat)
delimicno sprecili. Supstanca C, koja je inhibitor adenozin monofosfatom aktivirane
protein kinaze AMPK (engl. AMPactivated protein kinase), je smanjila antiglioma
efekat metformina dok je AMPK agonista AICAR (engl. 5-Aminoimidazole-4-
carboxamide ribonucleotide) imitirao pomenuti efekat. Primarni astrociti pacova su bili
u potpunosti otporni na antiproliferativno i proapoptotsko dejstvo metformina.
Dalje je ispitivan in vitro uticaj metformina na antikancersku aktivnost dobro
poznatog hemoterapeutika cisplatina. Iako je sam metformin smanjio broj tumorskih
celija, iznenadujuce antagonizovao je citotoksicnost cisplatina u U251 celijama glioma.
Metformin je smanjio apoptotsku celijsku smrt indukovanu cisplatinom u U251
celijama glioma, tako što je smanjio oksidativni stres i aktivaciju kaspaza. Zapažena
citoprotekcija je ocigledno nezavisna od AMPK, jer metformin nije dalje povecao
aktivaciju AMPK indukovanu cisplatinom i drugi farmakološki aktivatori AMPK nisu
uspeli da inhibiraju apoptozu indukovanu cisplatinom. Sa druge strane, metformin je
indukovao aktivaciju Akt u celijama tretiranim cisplatinom, a inhibitor Akt (10-DEBC
hidrohlorid) ili fosfoinozitid 3-kinaze/Akt inhibitor (LY294002) su poništili
antioksidantna i antiapoptotska dejstva posredovana metforminom.
U odsustvu cisplatina in vitro i in vivo antimelanoma efekat metformina je
ispitivan, koristeci B16 celijsku liniju melanoma miša. Metformin je izazvao
zaustavljanje celijskog ciklusa u G2/M fazi, koje je povezano sa apoptotskom smrcu
celija melanoma. Indukcija oksidativnog stresa i depolarizacija membrane mitohondrija
su prethodili apoptozi posredovanoj metforminom za koju je pokazano, da je zavisna od
kaspaza. Metformin je povecao ekspresiju tumor supresornog proteina p53, dok je
smanjio nivo iRNK antiapoptotskog proteina Bcl-2.Tretman metforminom nije
stimulisao ekspresiju inhibitora celijskog ciklusa p21, dajuci indikaciju da p21 nije
neophodan za zapaženi blok celijskog ciklusa. Za antimelanoma delovanje metformina
izgleda da nije potrebna aktivacija AMPK, jer supstanca C nije uspela da povrati
vijabilitet B16 celija tretiranih metforminom. Metformin je indukovao autofagiju u B16
celijama, dok su inhibitori autofagije amonijum hlorid i vortmanin delimicno povratili
vijabilitet celija melanoma tretiranih metforminom, što ukazuje da je autofagija
indukovana metforminom citotoksicna. Konacno, oralna upotreba metformina dovela je
do znacajnog smanjenja velicine tumora u mišijem B16 melanoma modelu.
Rezultati dobijeni u odsustvu cisplatina na celijskim linijama melanoma i glioma
in vitro, kao i na mišijem modelu in vivo, ukazuju na potencijalnu primenu metformina
kao antikancerskog agensa u navedenim tumorima. Sa druge strane, u prisustvu
cisplatina pokazalo se da treba veoma pažljivo uzeti u razmatranje upotrebu metformina
kod pacijenata koji boluju od dijabetesa i kancera i primaju cisplatin, ili kao
potencijalne aduvantne terapije u hemoterapeutskim protokolima baziranim na
cisplatinu.
AB  - We investigated the effect of the well known antidiabetic drug metformin on the
viability of melanoma and glioma cell lines in vitro, in the absence and presence of
cisplatin. Also, we were interested in the effect of metformin on melanoma growth in
vivo.
In the absence of cisplatin on rat glioma cell line C6, we have shown for the first
time a dual antiglioma effect of metformin. In low-density cultures of the C6 rat glioma
cell line, metformin blocked the cell cycle progression in G0/G1 phase without inducing
significant cell death. In confluent C6 cultures, on the otherhand, metformin caused
massive induction of caspase dependent apoptosis associated with c-JunNterminalkinase
(JNK) activation, mitochondrial depolarization and oxidative stress.
Metformin-triggered apoptosis was completely prevented by agents that block
mitochondrial permeability transition (cyclosporin A) and oxygen radical production
(N-acetylcisteine), while the inhibitors of JNK activation (SP600125) or glycolysis
(sodium fluoride, iodoacetate) provided partial protection. The antiglioma effect of
metformin was reduced by compound C, an inhibitor of AMP activated protein kinase
(AMPK), and was mimicked by the AMPK agonist AICAR. Rat primary astrocytes
were completely resistant to the antiproliferative and proapoptotic action of metformin.
Further, it was investigated the influence of metformin on the in vitro anticancer
activity of the well-known chemotherapeutic agent cisplatin. Although metformin
reduced the number of tumour cells when applied alone, it surprisingly antagonized the
cytotoxicity of cisplatin towards U251 human glioma. In U251 glioma cells metformin
suppressed cisplatin-induced apoptotic cell death through inhibition of oxidative stress
and caspase activation. The observed cytoprotection was apparently AMPKindependent,
as metformin did not further increase cisplatin-induced AMPK activation
in U251 cells and other pharmacological AMPK activators failed to block cisplatinmediated
apoptosis. On the other hand, metformin induced Akt activation in cisplatintreated
cells and Akt inhibitor 10-DEBC hydrochloride or phosphoinositide 3-
kinase/Akt inhibitor LY294002 abolished metformin-mediated antioxidant and
antiapoptotic effects.
In the absence of cisplatin, in vitro and in vivo anti-melanoma effect of
antidiabetic drug metformin was investigated using B16 mouse melanoma cell line.
Metformin caused a G2/M cell cycle arrest associated with apoptotic death of melanoma
cells. Metformin-mediated apoptosis of melanoma cells was preceded by the induction
of oxidative stress and mitochondrial membrane depolarization. Metformin caused an
increase in the expression of tumor suppressorprotein p53 with concomitant decrease of
anti-apoptotic Bcl-2 mRNA levels. However, the treatment with metformin did not
stimulate expression of the cycle blocker p21, indicating that p21 was dispensable for
the observed cell cycle arrest. The activation of AMP-activated protein kinase (AMPK)
was not required for the anti-melanoma action of metformin, as AMPK inhibitor
compound C completely failed to restore viability of metformin-treated B16 cells.
Metformin induced autophagy in B16 cells, autophagy inhibitors ammonium chloride
and wortmannin partly restored the viability of metformin-treated melanoma cells,
indicating that metformin-induced autophagy is cytotoxic. Finally, oral administration
of metformin led to a significant reduction in tumor size in a B16 mouse melanoma
model.
Results obtained in cisplatin absence on melanoma and glioma cell lines in vitro
and mouse melanoma model in vivo, indicate the potential metformin application as
anticancer therapeutic in melanoma and glioma tumor. On the other hand, data in the
cisplatin presence warrant caution when considering metformin for treatment of diabetic
cancer patients receiving cisplatin, or as a potential adjuvant in cisplatin-based
chemotherapeutic regimens.
PB  - Belgrade: University of Belgrade, School of Medicine
T2  - University of Belgrade, School of Medicine
T1  - Uticaj metformina na apoptozu ćelija glioma i melanoma in vitro i na rast melanoma in vivo
T1  - The Effect of Metformin on Glioma and Melanoma Cell Apoptosis in vitro and Melanoma Growth in vivo
SP  - 1
EP  - 87
UR  - https://hdl.handle.net/21.15107/rcub_nardus_2460
ER  - 

@phdthesis{
author = "Janjetović, Kristina",
year = "2014",
abstract = "U ovoj disertaciji ispitivan je efekat antidijabetskog leka metformina na
apoptozu celijskih linija melanoma i glioma in vitro, u odsustvu i prisustvu
hemoterapeutika cisplatina. Takode smo bili zainteresovani za uticaj metformina na rast
melanoma in vivo.
U odsustvu cisplatina po prvi put je pokazan dvojan antiglioma efekat
metformina na celijskoj liniji glioma pacova C6. U celijskim kulturama glioma pacova
C6 male gustine metformin je zaustavio progresiju celijskog ciklusa u G0/G1 fazi, bez
znacajnog povecanja celijske smrti. Sa druge strane, u konfluentnim kulturama C6 celija
metformin je izazvao izuzetno povecanje apoptoze koja je zavisna od kaspaza,
depolarizacije mitohondrija, oksidativnog stresa i povezana sa aktivacijom JNK (engl.
c-Jun N-terminal kinase). Apoptoza indukovana metforminom je u potpunosti sprecena
supstancama koje blokiraju promenu propustljivosti membrane mitohondrija
(ciklosporin A) i produkciju reaktivnih kiseonicnih vrsta (N-acetilcistein), dok su je
inhibitori aktivacije JNK (SP600125) ili glikolize (natrijumfluorid, jodoacetat)
delimicno sprecili. Supstanca C, koja je inhibitor adenozin monofosfatom aktivirane
protein kinaze AMPK (engl. AMPactivated protein kinase), je smanjila antiglioma
efekat metformina dok je AMPK agonista AICAR (engl. 5-Aminoimidazole-4-
carboxamide ribonucleotide) imitirao pomenuti efekat. Primarni astrociti pacova su bili
u potpunosti otporni na antiproliferativno i proapoptotsko dejstvo metformina.
Dalje je ispitivan in vitro uticaj metformina na antikancersku aktivnost dobro
poznatog hemoterapeutika cisplatina. Iako je sam metformin smanjio broj tumorskih
celija, iznenadujuce antagonizovao je citotoksicnost cisplatina u U251 celijama glioma.
Metformin je smanjio apoptotsku celijsku smrt indukovanu cisplatinom u U251
celijama glioma, tako što je smanjio oksidativni stres i aktivaciju kaspaza. Zapažena
citoprotekcija je ocigledno nezavisna od AMPK, jer metformin nije dalje povecao
aktivaciju AMPK indukovanu cisplatinom i drugi farmakološki aktivatori AMPK nisu
uspeli da inhibiraju apoptozu indukovanu cisplatinom. Sa druge strane, metformin je
indukovao aktivaciju Akt u celijama tretiranim cisplatinom, a inhibitor Akt (10-DEBC
hidrohlorid) ili fosfoinozitid 3-kinaze/Akt inhibitor (LY294002) su poništili
antioksidantna i antiapoptotska dejstva posredovana metforminom.
U odsustvu cisplatina in vitro i in vivo antimelanoma efekat metformina je
ispitivan, koristeci B16 celijsku liniju melanoma miša. Metformin je izazvao
zaustavljanje celijskog ciklusa u G2/M fazi, koje je povezano sa apoptotskom smrcu
celija melanoma. Indukcija oksidativnog stresa i depolarizacija membrane mitohondrija
su prethodili apoptozi posredovanoj metforminom za koju je pokazano, da je zavisna od
kaspaza. Metformin je povecao ekspresiju tumor supresornog proteina p53, dok je
smanjio nivo iRNK antiapoptotskog proteina Bcl-2.Tretman metforminom nije
stimulisao ekspresiju inhibitora celijskog ciklusa p21, dajuci indikaciju da p21 nije
neophodan za zapaženi blok celijskog ciklusa. Za antimelanoma delovanje metformina
izgleda da nije potrebna aktivacija AMPK, jer supstanca C nije uspela da povrati
vijabilitet B16 celija tretiranih metforminom. Metformin je indukovao autofagiju u B16
celijama, dok su inhibitori autofagije amonijum hlorid i vortmanin delimicno povratili
vijabilitet celija melanoma tretiranih metforminom, što ukazuje da je autofagija
indukovana metforminom citotoksicna. Konacno, oralna upotreba metformina dovela je
do znacajnog smanjenja velicine tumora u mišijem B16 melanoma modelu.
Rezultati dobijeni u odsustvu cisplatina na celijskim linijama melanoma i glioma
in vitro, kao i na mišijem modelu in vivo, ukazuju na potencijalnu primenu metformina
kao antikancerskog agensa u navedenim tumorima. Sa druge strane, u prisustvu
cisplatina pokazalo se da treba veoma pažljivo uzeti u razmatranje upotrebu metformina
kod pacijenata koji boluju od dijabetesa i kancera i primaju cisplatin, ili kao
potencijalne aduvantne terapije u hemoterapeutskim protokolima baziranim na
cisplatinu., We investigated the effect of the well known antidiabetic drug metformin on the
viability of melanoma and glioma cell lines in vitro, in the absence and presence of
cisplatin. Also, we were interested in the effect of metformin on melanoma growth in
vivo.
In the absence of cisplatin on rat glioma cell line C6, we have shown for the first
time a dual antiglioma effect of metformin. In low-density cultures of the C6 rat glioma
cell line, metformin blocked the cell cycle progression in G0/G1 phase without inducing
significant cell death. In confluent C6 cultures, on the otherhand, metformin caused
massive induction of caspase dependent apoptosis associated with c-JunNterminalkinase
(JNK) activation, mitochondrial depolarization and oxidative stress.
Metformin-triggered apoptosis was completely prevented by agents that block
mitochondrial permeability transition (cyclosporin A) and oxygen radical production
(N-acetylcisteine), while the inhibitors of JNK activation (SP600125) or glycolysis
(sodium fluoride, iodoacetate) provided partial protection. The antiglioma effect of
metformin was reduced by compound C, an inhibitor of AMP activated protein kinase
(AMPK), and was mimicked by the AMPK agonist AICAR. Rat primary astrocytes
were completely resistant to the antiproliferative and proapoptotic action of metformin.
Further, it was investigated the influence of metformin on the in vitro anticancer
activity of the well-known chemotherapeutic agent cisplatin. Although metformin
reduced the number of tumour cells when applied alone, it surprisingly antagonized the
cytotoxicity of cisplatin towards U251 human glioma. In U251 glioma cells metformin
suppressed cisplatin-induced apoptotic cell death through inhibition of oxidative stress
and caspase activation. The observed cytoprotection was apparently AMPKindependent,
as metformin did not further increase cisplatin-induced AMPK activation
in U251 cells and other pharmacological AMPK activators failed to block cisplatinmediated
apoptosis. On the other hand, metformin induced Akt activation in cisplatintreated
cells and Akt inhibitor 10-DEBC hydrochloride or phosphoinositide 3-
kinase/Akt inhibitor LY294002 abolished metformin-mediated antioxidant and
antiapoptotic effects.
In the absence of cisplatin, in vitro and in vivo anti-melanoma effect of
antidiabetic drug metformin was investigated using B16 mouse melanoma cell line.
Metformin caused a G2/M cell cycle arrest associated with apoptotic death of melanoma
cells. Metformin-mediated apoptosis of melanoma cells was preceded by the induction
of oxidative stress and mitochondrial membrane depolarization. Metformin caused an
increase in the expression of tumor suppressorprotein p53 with concomitant decrease of
anti-apoptotic Bcl-2 mRNA levels. However, the treatment with metformin did not
stimulate expression of the cycle blocker p21, indicating that p21 was dispensable for
the observed cell cycle arrest. The activation of AMP-activated protein kinase (AMPK)
was not required for the anti-melanoma action of metformin, as AMPK inhibitor
compound C completely failed to restore viability of metformin-treated B16 cells.
Metformin induced autophagy in B16 cells, autophagy inhibitors ammonium chloride
and wortmannin partly restored the viability of metformin-treated melanoma cells,
indicating that metformin-induced autophagy is cytotoxic. Finally, oral administration
of metformin led to a significant reduction in tumor size in a B16 mouse melanoma
model.
Results obtained in cisplatin absence on melanoma and glioma cell lines in vitro
and mouse melanoma model in vivo, indicate the potential metformin application as
anticancer therapeutic in melanoma and glioma tumor. On the other hand, data in the
cisplatin presence warrant caution when considering metformin for treatment of diabetic
cancer patients receiving cisplatin, or as a potential adjuvant in cisplatin-based
chemotherapeutic regimens.",
publisher = "Belgrade: University of Belgrade, School of Medicine",
journal = "University of Belgrade, School of Medicine",
title = "Uticaj metformina na apoptozu ćelija glioma i melanoma in vitro i na rast melanoma in vivo, The Effect of Metformin on Glioma and Melanoma Cell Apoptosis in vitro and Melanoma Growth in vivo",
pages = "1-87",
url = "https://hdl.handle.net/21.15107/rcub_nardus_2460"
}

Janjetović, K.. (2014). Uticaj metformina na apoptozu ćelija glioma i melanoma in vitro i na rast melanoma in vivo. in University of Belgrade, School of Medicine
Belgrade: University of Belgrade, School of Medicine., 1-87.
https://hdl.handle.net/21.15107/rcub_nardus_2460

Janjetović K. Uticaj metformina na apoptozu ćelija glioma i melanoma in vitro i na rast melanoma in vivo. in University of Belgrade, School of Medicine. 2014;:1-87.
https://hdl.handle.net/21.15107/rcub_nardus_2460 .

Janjetović, Kristina, "Uticaj metformina na apoptozu ćelija glioma i melanoma in vitro i na rast melanoma in vivo" in University of Belgrade, School of Medicine (2014):1-87,
https://hdl.handle.net/21.15107/rcub_nardus_2460 .

TY  - JOUR
AU  - Tovilović-Kovačević, Gordana
AU  - Zogović, Nevena
AU  - Šoškić, Vukić
AU  - Schrattenholz, Andre
AU  - Kostić-Rajačić, Slađana
AU  - Misirkić Marjanović, Maja
AU  - Janjetović, Kristina
AU  - Vučićević, Ljubica
AU  - Arsikin, Katarina
AU  - Harhaji-Trajković, Ljubica
AU  - Trajković, Vladimir
PY  - 2013
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6343
AB  - We investigated the ability of 19 recently synthesized arylpiperazine compounds to protect human SHSY5Y neuroblastoma cells from the neurotoxin 6-hydroxydopamine (6-OHDA). The compound with the most potent neuroprotective action was N-{3-[2-(4-phenyl-piperazin-1-yl)-ethyl]-phenyl}-picolinamide (6b), which reduced 6-OHDA-induced apoptotic death through stabilization of mitochondrial membrane and subsequent prevention of superoxide production, caspase activation and DNA fragmentation. 6-OHDA-triggered autophagic response was also reduced by 6b, which prevented inactivation of the main autophagy repressor mTOR, upregulation of proautophagic beclin-1, conversion of microtubule-associated protein 1 light chain 3 (LC3)-I to autophagosome-associated LC3-II, as well as intracytoplasmic acidification induced by 6-OHDA. The inhibition of autophagy using LC3b gene silencing or pharmacological autophagy blockers 3-methyladenine or bafilomycin A1, mimicked the cytoprotective effect of 6b. While the treatment with 6b had no effect on the phosphorylation of proapoptotic MAP kinases ERK and JNK, it markedly increased the phosphorylation of the prosurvival kinase Akt in 6-OHDA-treated cells. Akt inhibitor DEBC or RNA interference-mediated Akt silencing reduced the ability of 6b to block 6-OHDA-triggered apoptotic and autophagic responses, thus confirming their dependency on Akt activation. The cytoprotective effect of 6b was also observed in 6-OHDA-treated neuronal PC12 cells, but not in SH-SY5Y or PC12 cells exposed to 1-methyl-4-phenylpyridinium, indicating that the observed neuroprotection was dependent on the cytotoxic stimulus. Because of the ability to prevent 6-OHDA induced apoptotic/autophagic cell death through activation of Akt, the investigated arylpiperazines could be potential candidates for treatment of neurodegenerative diseases.
PB  - Elsevier Ltd.
T2  - Neuropharmacology
T1  - Arylpiperazine-mediated activation of Akt protects SH-SY5Y neuroblastoma cells from 6-hydroxydopamine-induced apoptotic and autophagic death
VL  - 72
DO  - 10.1016/j.neuropharm.2013.04.037
SP  - 224
EP  - 235
ER  - 

@article{
author = "Tovilović-Kovačević, Gordana and Zogović, Nevena and Šoškić, Vukić and Schrattenholz, Andre and Kostić-Rajačić, Slađana and Misirkić Marjanović, Maja and Janjetović, Kristina and Vučićević, Ljubica and Arsikin, Katarina and Harhaji-Trajković, Ljubica and Trajković, Vladimir",
year = "2013",
abstract = "We investigated the ability of 19 recently synthesized arylpiperazine compounds to protect human SHSY5Y neuroblastoma cells from the neurotoxin 6-hydroxydopamine (6-OHDA). The compound with the most potent neuroprotective action was N-{3-[2-(4-phenyl-piperazin-1-yl)-ethyl]-phenyl}-picolinamide (6b), which reduced 6-OHDA-induced apoptotic death through stabilization of mitochondrial membrane and subsequent prevention of superoxide production, caspase activation and DNA fragmentation. 6-OHDA-triggered autophagic response was also reduced by 6b, which prevented inactivation of the main autophagy repressor mTOR, upregulation of proautophagic beclin-1, conversion of microtubule-associated protein 1 light chain 3 (LC3)-I to autophagosome-associated LC3-II, as well as intracytoplasmic acidification induced by 6-OHDA. The inhibition of autophagy using LC3b gene silencing or pharmacological autophagy blockers 3-methyladenine or bafilomycin A1, mimicked the cytoprotective effect of 6b. While the treatment with 6b had no effect on the phosphorylation of proapoptotic MAP kinases ERK and JNK, it markedly increased the phosphorylation of the prosurvival kinase Akt in 6-OHDA-treated cells. Akt inhibitor DEBC or RNA interference-mediated Akt silencing reduced the ability of 6b to block 6-OHDA-triggered apoptotic and autophagic responses, thus confirming their dependency on Akt activation. The cytoprotective effect of 6b was also observed in 6-OHDA-treated neuronal PC12 cells, but not in SH-SY5Y or PC12 cells exposed to 1-methyl-4-phenylpyridinium, indicating that the observed neuroprotection was dependent on the cytotoxic stimulus. Because of the ability to prevent 6-OHDA induced apoptotic/autophagic cell death through activation of Akt, the investigated arylpiperazines could be potential candidates for treatment of neurodegenerative diseases.",
publisher = "Elsevier Ltd.",
journal = "Neuropharmacology",
title = "Arylpiperazine-mediated activation of Akt protects SH-SY5Y neuroblastoma cells from 6-hydroxydopamine-induced apoptotic and autophagic death",
volume = "72",
doi = "10.1016/j.neuropharm.2013.04.037",
pages = "224-235"
}

Tovilović-Kovačević, G., Zogović, N., Šoškić, V., Schrattenholz, A., Kostić-Rajačić, S., Misirkić Marjanović, M., Janjetović, K., Vučićević, L., Arsikin, K., Harhaji-Trajković, L.,& Trajković, V.. (2013). Arylpiperazine-mediated activation of Akt protects SH-SY5Y neuroblastoma cells from 6-hydroxydopamine-induced apoptotic and autophagic death. in Neuropharmacology
Elsevier Ltd.., 72, 224-235.
https://doi.org/10.1016/j.neuropharm.2013.04.037

Tovilović-Kovačević G, Zogović N, Šoškić V, Schrattenholz A, Kostić-Rajačić S, Misirkić Marjanović M, Janjetović K, Vučićević L, Arsikin K, Harhaji-Trajković L, Trajković V. Arylpiperazine-mediated activation of Akt protects SH-SY5Y neuroblastoma cells from 6-hydroxydopamine-induced apoptotic and autophagic death. in Neuropharmacology. 2013;72:224-235.
doi:10.1016/j.neuropharm.2013.04.037 .

Tovilović-Kovačević, Gordana, Zogović, Nevena, Šoškić, Vukić, Schrattenholz, Andre, Kostić-Rajačić, Slađana, Misirkić Marjanović, Maja, Janjetović, Kristina, Vučićević, Ljubica, Arsikin, Katarina, Harhaji-Trajković, Ljubica, Trajković, Vladimir, "Arylpiperazine-mediated activation of Akt protects SH-SY5Y neuroblastoma cells from 6-hydroxydopamine-induced apoptotic and autophagic death" in Neuropharmacology, 72 (2013):224-235,
https://doi.org/10.1016/j.neuropharm.2013.04.037 . .

TY  - CONF
AU  - Zogović, Nevena
AU  - Tovilović-Kovačević, Gordana
AU  - Misirkić Marjanović, Maja
AU  - Janjetović, Kristina
AU  - Vučićević, Ljubica
AU  - Trajković, Vladimir
PY  - 2013
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6354
AB  - Introduction: Neural differentiation involves
intracellular signaling-controlled maturation of neural
progenitors into cells with fully developed neuronal
phenotype.
Aim: We explored the interplay between the
adenosine monophosphate-activated protein kinase
(AMPK), extracellular signal-regulated kinase (ERK) and
autophagy in phorbol myristate acetate (PMA)-induced
differentiation of SH-SY5Y human neuroblastoma cells.
Methods: The levels of neuronal marker expression
and acidification of autophagic compartments were
determined by flow cytometry of cells labeled with
appropriate antibodies and acridine orange, respectively.
The activation (phosphorylation) of AMPK and ERK, as
well as the levels of autophagic proteins beclin-1, Atg7,
microtubule-associated protein light chain 3 (LC3) and p62,
were assessed using immunoblot. RNA interference was
used for AMPK and LC3 knockdown.
Results: PMA initiated autophagic response in SH-
SY5Y cells simultaneously with activation of AMPK, a
major intracellular energy sensor, and ERK, a kinase
involved in cell proliferation and differentiation.
Pharmacological inhibition of AMPK or AMPK gene
silencing attenuated differentiation of SH-SY5Y cells, as
well as PMA-induced ERK activation and autophagy. A
selective pharmacological blockade of ERK prevented
PMA-induced neuronal differentiation and autophagy
induction, without affecting AMPK phosphorylation. On the
other hand, the inhibition of autophagy downstream of
AMPK/ERK activation, either by pharmacological agents or
LC3 knockdown, actually promoted the expression of
neuronal markers, thus indicating a role for autophagy in
suppression of PMA-induced differentiation of SH-SY5Y
cells.
Conclusion: PMA-induced differentiation of SH-
SY5Y cells depends on a complex interplay between
AMPK, ERK and autophagy, where AMPK and ERK
promote differentiation independently of autophagy, while
simultaneously inhibiting differentiation process through
autophagy-dependent mechanisms.
AB  - Uvod: Diferencijacija neurona je proces
kontrolisan od strane nekoliko unutarćelijskih signala. U
toku diferencijacije dolazi do potpunog sazrevanja
progenitorskih ćelija u neurone.
Cilj: Cilj ovog rada je bio da se ispita uloga protein
kinaze regulisane adenozin monofosfatom (AMPK), kinaze
regulisane vanćelijskim signalima (ERK) i autofagije tokom
diferencijacije humanih neuroblastoma SH-SY5Y izazvane
forbol miristat acetatom (PMA).
Metode: Ekspresija neuronskih markera i
autofagija su praćene pomoću protočnog citofluorimetra
nakon bojenja ćelija sa odgovarajućim antitelima, odnosno
akridin oranžom. Aktivnosti AMPK, ERK, beklina, Atg7,
proteina lakog lanca 3 povezanog sa mikrotubulima (LC3),
p62, p70S6K i aktina su odreñene pomoću imunoblota.
Utišavanje AMPK i LC3 gena je izvedeno pomoću malih
interferirajućih RNK.
Rezultati: Istovremeno sa započinjanjem
autofagije, PMA je aktivirao AMPK protein, glavni
energetski senzor u ćeliji, i ERK kinazu, zaduženu za
regulaciju diferencijacije i proliferacije. Farmakološka
inhibicija AMPK i utišavanje gena za AMPK usporili su
diferencijaciju SH-SY5Y ćelija, i inhibirali su aktivaciju
ERK kinaze i autofagiju izazvane pomoću PMA. Blokiranje
aktivnosti ERK proteina pomoću specifičnog inhibitora
značajno je usporilo diferencijaciju SH-SY5Y ćelija i
autofagiju izazvane posredstvom PMA, bez uticaja na
aktivnost AMPK. Sa druge strane, inhibicija autofagije
nishodno od AMPK/ERK (farmakološka ili utišavanjem
gena za LC3) je povećala ekspresiju neuronskih markera,
što ukazuje na činjenicu da autofagija izazvana pomoću
PMA najverovatnije suprimira diferencijaciju SH-SY5Y
ćelija.
Zaključak: Diferencijaciju SH-SY5Y ćelija
izazvanu posredstvom PMA pospešuju AMPK i ERK
proteini nezavisno od autofagnog procesa. Istovremeno oba
molekula inhibiraju diferencijaciju preko mehanizama
zavisnih od autofagije.
PB  - Belgrade : Serbian Neuroscience Society
C3  - 6th SNS Serbian Neuroscience Society Congress: book of abstracts; 2013 Nov 14-16; Belgrade, Serbia
T1  - AMPK and ERK regulate phorbol myristate acetate induced differentiation of SH-SY5Y neuroblastoma cells trough autophagy-dependent and –independent mehanisms
T1  - Protein kinaza regulisana adenozin monofosfatom i kinaza regulisana vanćelijskim signalima regulišu diferencijaciju SH-SY5Y ćelija neuroblastoma izazvanu forbol miristat acetatom preko mehanizama zavisnih i nezavisnih od autofagije
SP  - 58
EP  - 58
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_6354
ER  - 

@conference{
editor = "Kanazir, Selma, Savić, Danijela, Isaković, Aleksandra",
author = "Zogović, Nevena and Tovilović-Kovačević, Gordana and Misirkić Marjanović, Maja and Janjetović, Kristina and Vučićević, Ljubica and Trajković, Vladimir",
year = "2013",
abstract = "Introduction: Neural differentiation involves
intracellular signaling-controlled maturation of neural
progenitors into cells with fully developed neuronal
phenotype.
Aim: We explored the interplay between the
adenosine monophosphate-activated protein kinase
(AMPK), extracellular signal-regulated kinase (ERK) and
autophagy in phorbol myristate acetate (PMA)-induced
differentiation of SH-SY5Y human neuroblastoma cells.
Methods: The levels of neuronal marker expression
and acidification of autophagic compartments were
determined by flow cytometry of cells labeled with
appropriate antibodies and acridine orange, respectively.
The activation (phosphorylation) of AMPK and ERK, as
well as the levels of autophagic proteins beclin-1, Atg7,
microtubule-associated protein light chain 3 (LC3) and p62,
were assessed using immunoblot. RNA interference was
used for AMPK and LC3 knockdown.
Results: PMA initiated autophagic response in SH-
SY5Y cells simultaneously with activation of AMPK, a
major intracellular energy sensor, and ERK, a kinase
involved in cell proliferation and differentiation.
Pharmacological inhibition of AMPK or AMPK gene
silencing attenuated differentiation of SH-SY5Y cells, as
well as PMA-induced ERK activation and autophagy. A
selective pharmacological blockade of ERK prevented
PMA-induced neuronal differentiation and autophagy
induction, without affecting AMPK phosphorylation. On the
other hand, the inhibition of autophagy downstream of
AMPK/ERK activation, either by pharmacological agents or
LC3 knockdown, actually promoted the expression of
neuronal markers, thus indicating a role for autophagy in
suppression of PMA-induced differentiation of SH-SY5Y
cells.
Conclusion: PMA-induced differentiation of SH-
SY5Y cells depends on a complex interplay between
AMPK, ERK and autophagy, where AMPK and ERK
promote differentiation independently of autophagy, while
simultaneously inhibiting differentiation process through
autophagy-dependent mechanisms., Uvod: Diferencijacija neurona je proces
kontrolisan od strane nekoliko unutarćelijskih signala. U
toku diferencijacije dolazi do potpunog sazrevanja
progenitorskih ćelija u neurone.
Cilj: Cilj ovog rada je bio da se ispita uloga protein
kinaze regulisane adenozin monofosfatom (AMPK), kinaze
regulisane vanćelijskim signalima (ERK) i autofagije tokom
diferencijacije humanih neuroblastoma SH-SY5Y izazvane
forbol miristat acetatom (PMA).
Metode: Ekspresija neuronskih markera i
autofagija su praćene pomoću protočnog citofluorimetra
nakon bojenja ćelija sa odgovarajućim antitelima, odnosno
akridin oranžom. Aktivnosti AMPK, ERK, beklina, Atg7,
proteina lakog lanca 3 povezanog sa mikrotubulima (LC3),
p62, p70S6K i aktina su odreñene pomoću imunoblota.
Utišavanje AMPK i LC3 gena je izvedeno pomoću malih
interferirajućih RNK.
Rezultati: Istovremeno sa započinjanjem
autofagije, PMA je aktivirao AMPK protein, glavni
energetski senzor u ćeliji, i ERK kinazu, zaduženu za
regulaciju diferencijacije i proliferacije. Farmakološka
inhibicija AMPK i utišavanje gena za AMPK usporili su
diferencijaciju SH-SY5Y ćelija, i inhibirali su aktivaciju
ERK kinaze i autofagiju izazvane pomoću PMA. Blokiranje
aktivnosti ERK proteina pomoću specifičnog inhibitora
značajno je usporilo diferencijaciju SH-SY5Y ćelija i
autofagiju izazvane posredstvom PMA, bez uticaja na
aktivnost AMPK. Sa druge strane, inhibicija autofagije
nishodno od AMPK/ERK (farmakološka ili utišavanjem
gena za LC3) je povećala ekspresiju neuronskih markera,
što ukazuje na činjenicu da autofagija izazvana pomoću
PMA najverovatnije suprimira diferencijaciju SH-SY5Y
ćelija.
Zaključak: Diferencijaciju SH-SY5Y ćelija
izazvanu posredstvom PMA pospešuju AMPK i ERK
proteini nezavisno od autofagnog procesa. Istovremeno oba
molekula inhibiraju diferencijaciju preko mehanizama
zavisnih od autofagije.",
publisher = "Belgrade : Serbian Neuroscience Society",
journal = "6th SNS Serbian Neuroscience Society Congress: book of abstracts; 2013 Nov 14-16; Belgrade, Serbia",
title = "AMPK and ERK regulate phorbol myristate acetate induced differentiation of SH-SY5Y neuroblastoma cells trough autophagy-dependent and –independent mehanisms, Protein kinaza regulisana adenozin monofosfatom i kinaza regulisana vanćelijskim signalima regulišu diferencijaciju SH-SY5Y ćelija neuroblastoma izazvanu forbol miristat acetatom preko mehanizama zavisnih i nezavisnih od autofagije",
pages = "58-58",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_6354"
}

Kanazir, S., Savić, D., Isaković, A., Zogović, N., Tovilović-Kovačević, G., Misirkić Marjanović, M., Janjetović, K., Vučićević, L.,& Trajković, V.. (2013). AMPK and ERK regulate phorbol myristate acetate induced differentiation of SH-SY5Y neuroblastoma cells trough autophagy-dependent and –independent mehanisms. in 6th SNS Serbian Neuroscience Society Congress: book of abstracts; 2013 Nov 14-16; Belgrade, Serbia
Belgrade : Serbian Neuroscience Society., 58-58.
https://hdl.handle.net/21.15107/rcub_ibiss_6354

Kanazir S, Savić D, Isaković A, Zogović N, Tovilović-Kovačević G, Misirkić Marjanović M, Janjetović K, Vučićević L, Trajković V. AMPK and ERK regulate phorbol myristate acetate induced differentiation of SH-SY5Y neuroblastoma cells trough autophagy-dependent and –independent mehanisms. in 6th SNS Serbian Neuroscience Society Congress: book of abstracts; 2013 Nov 14-16; Belgrade, Serbia. 2013;:58-58.
https://hdl.handle.net/21.15107/rcub_ibiss_6354 .

Kanazir, Selma, Savić, Danijela, Isaković, Aleksandra, Zogović, Nevena, Tovilović-Kovačević, Gordana, Misirkić Marjanović, Maja, Janjetović, Kristina, Vučićević, Ljubica, Trajković, Vladimir, "AMPK and ERK regulate phorbol myristate acetate induced differentiation of SH-SY5Y neuroblastoma cells trough autophagy-dependent and –independent mehanisms" in 6th SNS Serbian Neuroscience Society Congress: book of abstracts; 2013 Nov 14-16; Belgrade, Serbia (2013):58-58,
https://hdl.handle.net/21.15107/rcub_ibiss_6354 .

TY  - JOUR
AU  - Pantović, Aleksandar C
AU  - Krstić, Aleksandra D
AU  - Janjetović, Kristina
AU  - Kocić, Jelena S
AU  - Harhaji-Trajković, Ljubica
AU  - Bugarski, Diana S
AU  - Trajković, Vladimir S
PY  - 2013
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/1064
AB  - We investigated the role of AMP-activated protein kinase (AMPK), Akt, mammalian target of rapamycin (mTOR), autophagy and their interplay in osteogenic differentiation of human dental pulp mesenchymal stem cells. The activation of various members of AMPK, Akt and mTOR signaling pathways and autophagy was analyzed by immunoblotting, while osteogenic differentiation was assessed by alkaline phosphatase staining and real-time RT-PCR/immunoblot quantification of osteocalcin, Runt-related transcription factor 2 and bone morphogenetic protein 2 mRNA and/or protein levels. Osteogenic differentiation of mesenchymal stem cells was associated with early (day 1) activation of AMPK and its target Raptor, coinciding with the inhibition of mTOR and its substrate p70S6 kinase. The early induction of autophagy was demonstrated by accumulation of autophagosome-bound LC3-11, upregulation of proautophagic,beclin-1 and a decrease in the selective autophagic target p62. This was followed by the late activation of Akt/mTOR at days 3-7 of differentiation. The RNA interference-mediated silencing of AMPK, mTOR or autophagy-essential LC3 beta, as well as the pharmacological inhibitors of AMPK (compound C), Akt (10-DEBC hydrochloride), mTOR (rapamycin) and autophagy (bafilomycin A1, chloroquine and ammonium chloride), each suppressed mesenchymal stem cell differentiation to osteoblasts. AMPK knockdown prevented early mTOR inhibition and autophagy induction, as well as late activation of Akt/mTOR signaling, while Ala inhibition suppressed mTOR activation without affecting AMPK phosphorylation. Our data indicate that AMPK controls osteogenic differentiation of human mesenchymal stem cells through both early mTOR inhibition-mediated autophagy and late activation of Akt/mTOR signaling axis. (C) 2012 Elsevier Inc. All rights reserved.
T2  - Bone
T1  - Coordinated time-dependent modulation of AMPK/Akt/mTOR signaling and autophagy controls osteogenic differentiation of human mesenchymal stem cells
IS  - 1
VL  - 52
DO  - 10.1016/j.bone.2012.10.024
SP  - 537
EP  - 531
ER  - 

@article{
author = "Pantović, Aleksandar C and Krstić, Aleksandra D and Janjetović, Kristina and Kocić, Jelena S and Harhaji-Trajković, Ljubica and Bugarski, Diana S and Trajković, Vladimir S",
year = "2013",
abstract = "We investigated the role of AMP-activated protein kinase (AMPK), Akt, mammalian target of rapamycin (mTOR), autophagy and their interplay in osteogenic differentiation of human dental pulp mesenchymal stem cells. The activation of various members of AMPK, Akt and mTOR signaling pathways and autophagy was analyzed by immunoblotting, while osteogenic differentiation was assessed by alkaline phosphatase staining and real-time RT-PCR/immunoblot quantification of osteocalcin, Runt-related transcription factor 2 and bone morphogenetic protein 2 mRNA and/or protein levels. Osteogenic differentiation of mesenchymal stem cells was associated with early (day 1) activation of AMPK and its target Raptor, coinciding with the inhibition of mTOR and its substrate p70S6 kinase. The early induction of autophagy was demonstrated by accumulation of autophagosome-bound LC3-11, upregulation of proautophagic,beclin-1 and a decrease in the selective autophagic target p62. This was followed by the late activation of Akt/mTOR at days 3-7 of differentiation. The RNA interference-mediated silencing of AMPK, mTOR or autophagy-essential LC3 beta, as well as the pharmacological inhibitors of AMPK (compound C), Akt (10-DEBC hydrochloride), mTOR (rapamycin) and autophagy (bafilomycin A1, chloroquine and ammonium chloride), each suppressed mesenchymal stem cell differentiation to osteoblasts. AMPK knockdown prevented early mTOR inhibition and autophagy induction, as well as late activation of Akt/mTOR signaling, while Ala inhibition suppressed mTOR activation without affecting AMPK phosphorylation. Our data indicate that AMPK controls osteogenic differentiation of human mesenchymal stem cells through both early mTOR inhibition-mediated autophagy and late activation of Akt/mTOR signaling axis. (C) 2012 Elsevier Inc. All rights reserved.",
journal = "Bone",
title = "Coordinated time-dependent modulation of AMPK/Akt/mTOR signaling and autophagy controls osteogenic differentiation of human mesenchymal stem cells",
number = "1",
volume = "52",
doi = "10.1016/j.bone.2012.10.024",
pages = "537-531"
}

Pantović, A. C., Krstić, A. D., Janjetović, K., Kocić, J. S., Harhaji-Trajković, L., Bugarski, D. S.,& Trajković, V. S.. (2013). Coordinated time-dependent modulation of AMPK/Akt/mTOR signaling and autophagy controls osteogenic differentiation of human mesenchymal stem cells. in Bone, 52(1), 537-531.
https://doi.org/10.1016/j.bone.2012.10.024

Pantović AC, Krstić AD, Janjetović K, Kocić JS, Harhaji-Trajković L, Bugarski DS, Trajković VS. Coordinated time-dependent modulation of AMPK/Akt/mTOR signaling and autophagy controls osteogenic differentiation of human mesenchymal stem cells. in Bone. 2013;52(1):537-531.
doi:10.1016/j.bone.2012.10.024 .

Pantović, Aleksandar C, Krstić, Aleksandra D, Janjetović, Kristina, Kocić, Jelena S, Harhaji-Trajković, Ljubica, Bugarski, Diana S, Trajković, Vladimir S, "Coordinated time-dependent modulation of AMPK/Akt/mTOR signaling and autophagy controls osteogenic differentiation of human mesenchymal stem cells" in Bone, 52, no. 1 (2013):537-531,
https://doi.org/10.1016/j.bone.2012.10.024 . .

TY  - JOUR
AU  - Stevanović, Darko
AU  - Trajković, Vladimir
AU  - Müller-Lühlhoff, Sabrina
AU  - Brandt, Elisabeth
AU  - Abplanalp, William
AU  - Bumke-Vogt, Christiane
AU  - Liehl, Beate
AU  - Wiedmer, Petra
AU  - Janjetović, Kristina
AU  - Starčević, Vesna
AU  - Pfeiffer, Andreas F.H.
AU  - Al-Hasani, Hadi
AU  - Tschöp, Matthias H.
AU  - Castañeda, Tamara R.
PY  - 2013
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6350
AB  - Signaling through the mammalian target of rapamycin complex 1 (mTORC1) and its effectors the S6-
kinases (S6K) in the hypothalamus is thought to be involved in nutrient sensing and control of food
intake. Given the anatomical proximity of this pathway to circuits for the hormone ghrelin, we investigated
the potential role of the mTORC1/S6K pathway in mediating the metabolic effects of ghrelin. We
found that ghrelin promoted phosphorylation of S6K1 in the mouse hypothalamic cell line N-41 and in
the rat hypothalamus after intracerebroventricular administration. Rapamycin, an inhibitor of mTORC1,
suppressed ghrelin-induced phosphorylation of hypothalamic S6K1 and increased food intake and insulin
in rats. Chronic peripheral administration of ghrelin induced a significant increase in body weight, fat
mass and food efficiency in wild-type and S6K2-knockout but not in S6K1-knockout mice. We therefore
propose that ghrelin-induced hyperphagia, adiposity and insulin secretion are controlled by a central nervous system involving the mTORC1/S6K1 pathway.
PB  - Elsevier
T2  - Molecular and Cellular Endocrinology
T1  - Ghrelin-induced food intake and adiposity depend on central mTORC1/S6K1 signaling
IS  - 1-2
VL  - 381
DO  - 10.1016/j.mce.2013.08.009
SP  - 280
EP  - 290
ER  - 

@article{
author = "Stevanović, Darko and Trajković, Vladimir and Müller-Lühlhoff, Sabrina and Brandt, Elisabeth and Abplanalp, William and Bumke-Vogt, Christiane and Liehl, Beate and Wiedmer, Petra and Janjetović, Kristina and Starčević, Vesna and Pfeiffer, Andreas F.H. and Al-Hasani, Hadi and Tschöp, Matthias H. and Castañeda, Tamara R.",
year = "2013",
abstract = "Signaling through the mammalian target of rapamycin complex 1 (mTORC1) and its effectors the S6-
kinases (S6K) in the hypothalamus is thought to be involved in nutrient sensing and control of food
intake. Given the anatomical proximity of this pathway to circuits for the hormone ghrelin, we investigated
the potential role of the mTORC1/S6K pathway in mediating the metabolic effects of ghrelin. We
found that ghrelin promoted phosphorylation of S6K1 in the mouse hypothalamic cell line N-41 and in
the rat hypothalamus after intracerebroventricular administration. Rapamycin, an inhibitor of mTORC1,
suppressed ghrelin-induced phosphorylation of hypothalamic S6K1 and increased food intake and insulin
in rats. Chronic peripheral administration of ghrelin induced a significant increase in body weight, fat
mass and food efficiency in wild-type and S6K2-knockout but not in S6K1-knockout mice. We therefore
propose that ghrelin-induced hyperphagia, adiposity and insulin secretion are controlled by a central nervous system involving the mTORC1/S6K1 pathway.",
publisher = "Elsevier",
journal = "Molecular and Cellular Endocrinology",
title = "Ghrelin-induced food intake and adiposity depend on central mTORC1/S6K1 signaling",
number = "1-2",
volume = "381",
doi = "10.1016/j.mce.2013.08.009",
pages = "280-290"
}

Stevanović, D., Trajković, V., Müller-Lühlhoff, S., Brandt, E., Abplanalp, W., Bumke-Vogt, C., Liehl, B., Wiedmer, P., Janjetović, K., Starčević, V., Pfeiffer, A. F.H., Al-Hasani, H., Tschöp, M. H.,& Castañeda, T. R.. (2013). Ghrelin-induced food intake and adiposity depend on central mTORC1/S6K1 signaling. in Molecular and Cellular Endocrinology
Elsevier., 381(1-2), 280-290.
https://doi.org/10.1016/j.mce.2013.08.009

Stevanović D, Trajković V, Müller-Lühlhoff S, Brandt E, Abplanalp W, Bumke-Vogt C, Liehl B, Wiedmer P, Janjetović K, Starčević V, Pfeiffer AF, Al-Hasani H, Tschöp MH, Castañeda TR. Ghrelin-induced food intake and adiposity depend on central mTORC1/S6K1 signaling. in Molecular and Cellular Endocrinology. 2013;381(1-2):280-290.
doi:10.1016/j.mce.2013.08.009 .

Stevanović, Darko, Trajković, Vladimir, Müller-Lühlhoff, Sabrina, Brandt, Elisabeth, Abplanalp, William, Bumke-Vogt, Christiane, Liehl, Beate, Wiedmer, Petra, Janjetović, Kristina, Starčević, Vesna, Pfeiffer, Andreas F.H., Al-Hasani, Hadi, Tschöp, Matthias H., Castañeda, Tamara R., "Ghrelin-induced food intake and adiposity depend on central mTORC1/S6K1 signaling" in Molecular and Cellular Endocrinology, 381, no. 1-2 (2013):280-290,
https://doi.org/10.1016/j.mce.2013.08.009 . .

TY  - JOUR
AU  - Tovilović-Kovačević, Gordana
AU  - Zogović, Nevena
AU  - Harhaji-Trajković, Ljubica
AU  - Misirkić Marjanović, Maja
AU  - Janjetović, Kristina
AU  - Vučićević, Ljubica
AU  - Kostić-Rajačić, Slađana
AU  - Schrattenholz, Andre
AU  - Isaković, Aleksandra
AU  - Šoškić, Vukić
AU  - Trajković, Vladimir
PY  - 2012
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6367
AB  - The protective ability of novel arylpiperazine-based dopaminergic ligands against nitric oxide (NO)-mediated neurotoxicity is investigated. The most potent neuroprotective arylpiperazine identified during the study was N-{4-[2-(4-phenyl-piperazin-1-yl)ethyl]-phenyl}picolinamide, which protected SH-SY5Y human neuron-like cells from the proapoptotic effect of NO donor sodium nitroprusside (SNP) by decreasing oxidative stress, mitochondrial membrane depolarization, caspase activation and subsequent phosphatydilserine externalization/DNA fragmentation. The protective effect was associated with the inhibition of proapoptotic (JNK, ERK, AMPK) and activation of antiapoptotic (Akt) signaling pathways, in the absence of interference with intracellular NO accumulation. The neuroprotective action of arylpiperazines was shown to be independent of dopamine receptor binding, as it was not affected by the high-affinity D₁/D₂ receptor blocker butaclamol. These results reported support the further study of arylpiperazines as potential neuroprotective agents.
PB  - John Wiley and Sons
T2  - ChemMedChem
T1  - Arylpiperazine dopamineric ligands protect neuroblastoma cells from nitric oxide (NO)-induced mitochondrial damage and apoptosis
IS  - 3
VL  - 7
DO  - 10.1002/cmdc.201100537
SP  - 495
EP  - 508
ER  - 

@article{
author = "Tovilović-Kovačević, Gordana and Zogović, Nevena and Harhaji-Trajković, Ljubica and Misirkić Marjanović, Maja and Janjetović, Kristina and Vučićević, Ljubica and Kostić-Rajačić, Slađana and Schrattenholz, Andre and Isaković, Aleksandra and Šoškić, Vukić and Trajković, Vladimir",
year = "2012",
abstract = "The protective ability of novel arylpiperazine-based dopaminergic ligands against nitric oxide (NO)-mediated neurotoxicity is investigated. The most potent neuroprotective arylpiperazine identified during the study was N-{4-[2-(4-phenyl-piperazin-1-yl)ethyl]-phenyl}picolinamide, which protected SH-SY5Y human neuron-like cells from the proapoptotic effect of NO donor sodium nitroprusside (SNP) by decreasing oxidative stress, mitochondrial membrane depolarization, caspase activation and subsequent phosphatydilserine externalization/DNA fragmentation. The protective effect was associated with the inhibition of proapoptotic (JNK, ERK, AMPK) and activation of antiapoptotic (Akt) signaling pathways, in the absence of interference with intracellular NO accumulation. The neuroprotective action of arylpiperazines was shown to be independent of dopamine receptor binding, as it was not affected by the high-affinity D₁/D₂ receptor blocker butaclamol. These results reported support the further study of arylpiperazines as potential neuroprotective agents.",
publisher = "John Wiley and Sons",
journal = "ChemMedChem",
title = "Arylpiperazine dopamineric ligands protect neuroblastoma cells from nitric oxide (NO)-induced mitochondrial damage and apoptosis",
number = "3",
volume = "7",
doi = "10.1002/cmdc.201100537",
pages = "495-508"
}

Tovilović-Kovačević, G., Zogović, N., Harhaji-Trajković, L., Misirkić Marjanović, M., Janjetović, K., Vučićević, L., Kostić-Rajačić, S., Schrattenholz, A., Isaković, A., Šoškić, V.,& Trajković, V.. (2012). Arylpiperazine dopamineric ligands protect neuroblastoma cells from nitric oxide (NO)-induced mitochondrial damage and apoptosis. in ChemMedChem
John Wiley and Sons., 7(3), 495-508.
https://doi.org/10.1002/cmdc.201100537

Tovilović-Kovačević G, Zogović N, Harhaji-Trajković L, Misirkić Marjanović M, Janjetović K, Vučićević L, Kostić-Rajačić S, Schrattenholz A, Isaković A, Šoškić V, Trajković V. Arylpiperazine dopamineric ligands protect neuroblastoma cells from nitric oxide (NO)-induced mitochondrial damage and apoptosis. in ChemMedChem. 2012;7(3):495-508.
doi:10.1002/cmdc.201100537 .

Tovilović-Kovačević, Gordana, Zogović, Nevena, Harhaji-Trajković, Ljubica, Misirkić Marjanović, Maja, Janjetović, Kristina, Vučićević, Ljubica, Kostić-Rajačić, Slađana, Schrattenholz, Andre, Isaković, Aleksandra, Šoškić, Vukić, Trajković, Vladimir, "Arylpiperazine dopamineric ligands protect neuroblastoma cells from nitric oxide (NO)-induced mitochondrial damage and apoptosis" in ChemMedChem, 7, no. 3 (2012):495-508,
https://doi.org/10.1002/cmdc.201100537 . .

TY  - JOUR
AU  - Misirkić Marjanović, Maja
AU  - Janjetović, Kristina
AU  - Vučićević, Ljubica
AU  - Tovilović-Kovačević, Gordana
AU  - Ristić, Biljana Z
AU  - Vilimanović, Uros
AU  - Harhaji-Trajković, Ljubica
AU  - Sumarac-Dumanović, Mirjana S
AU  - Micić, Dragan D
AU  - Bumbaširević, Vladimir Z
AU  - Trajković, Vladimir S
PY  - 2012
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/1232
AB  - The role of autophagy, a process in which the cell self-digests its own components, was investigated in glioma cell death induced by the hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase-inhibiting drug simvastatin. Induction of autophagy and activation of autophagy-regulating signalling pathways were analyzed by immunoblotting. Flow cytometry/fluorescent microscopy was used to assess autophagy-associated intracellular acidification and apoptotic markers (phosphatidylserine exposure, DNA fragmentation and caspase activation). Cell viability was determined by crystal violet, MTT or LDH release assay. Simvastatin treatment of U251 and C6 glioma cell lines caused the appearance of autophagolysosome-like intracytoplasmic acidic vesicles. The induction of autophagy in U251 cells was confirmed by the upregulation of autophagosome-associated LC3-II and pro-autophagic beclin-1, as well as by the downregulation of the selective autophagic target p62. Simvastatin induced the activation of AMP-activated protein kinase (AMPK) and its target Raptor, while simultaneously downregulating activation of Akt. Mammalian target of rapamycin (mTOR). a major AMPK/Akt downstream target and a major negative autophagy regulator, and its substrate p70 S6 kinase 1 were also inhibited by simvastatin. Mevalonate, the product of HMG-CoA reductase enzymatic activity, AMPK siRNA or pharmacological inactivation of AMPK with compound C suppressed, while the inhibitors of Akt (10-DEBC hydrochloride) and mTOR (rapamycin) mimicked autophagy induction by simvastatin. Inhibition of autophagy with bafilomycin A1, 3-methyladenine and LC3 beta shRNA, as well as AMPK inhibition with compound C or AMPK siRNA, markedly increased apoptotic death of simvastatin-treated U251 cells. These data suggest that inhibition of AMPK-depenclent autophagic response might sensitize glioma cells to statin-induced apoptotic death. (C) 2011 Elsevier Ltd. All rights reserved.
T2  - Pharmacological Research
T1  - Inhibition of AMPK-dependent autophagy enhances in vitro antiglioma effect of simvastatin
IS  - 1
VL  - 65
EP  - 119
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_1232
ER  - 

@article{
author = "Misirkić Marjanović, Maja and Janjetović, Kristina and Vučićević, Ljubica and Tovilović-Kovačević, Gordana and Ristić, Biljana Z and Vilimanović, Uros and Harhaji-Trajković, Ljubica and Sumarac-Dumanović, Mirjana S and Micić, Dragan D and Bumbaširević, Vladimir Z and Trajković, Vladimir S",
year = "2012",
abstract = "The role of autophagy, a process in which the cell self-digests its own components, was investigated in glioma cell death induced by the hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase-inhibiting drug simvastatin. Induction of autophagy and activation of autophagy-regulating signalling pathways were analyzed by immunoblotting. Flow cytometry/fluorescent microscopy was used to assess autophagy-associated intracellular acidification and apoptotic markers (phosphatidylserine exposure, DNA fragmentation and caspase activation). Cell viability was determined by crystal violet, MTT or LDH release assay. Simvastatin treatment of U251 and C6 glioma cell lines caused the appearance of autophagolysosome-like intracytoplasmic acidic vesicles. The induction of autophagy in U251 cells was confirmed by the upregulation of autophagosome-associated LC3-II and pro-autophagic beclin-1, as well as by the downregulation of the selective autophagic target p62. Simvastatin induced the activation of AMP-activated protein kinase (AMPK) and its target Raptor, while simultaneously downregulating activation of Akt. Mammalian target of rapamycin (mTOR). a major AMPK/Akt downstream target and a major negative autophagy regulator, and its substrate p70 S6 kinase 1 were also inhibited by simvastatin. Mevalonate, the product of HMG-CoA reductase enzymatic activity, AMPK siRNA or pharmacological inactivation of AMPK with compound C suppressed, while the inhibitors of Akt (10-DEBC hydrochloride) and mTOR (rapamycin) mimicked autophagy induction by simvastatin. Inhibition of autophagy with bafilomycin A1, 3-methyladenine and LC3 beta shRNA, as well as AMPK inhibition with compound C or AMPK siRNA, markedly increased apoptotic death of simvastatin-treated U251 cells. These data suggest that inhibition of AMPK-depenclent autophagic response might sensitize glioma cells to statin-induced apoptotic death. (C) 2011 Elsevier Ltd. All rights reserved.",
journal = "Pharmacological Research",
title = "Inhibition of AMPK-dependent autophagy enhances in vitro antiglioma effect of simvastatin",
number = "1",
volume = "65",
pages = "119",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_1232"
}

Misirkić Marjanović, M., Janjetović, K., Vučićević, L., Tovilović-Kovačević, G., Ristić, B. Z., Vilimanović, U., Harhaji-Trajković, L., Sumarac-Dumanović, M. S., Micić, D. D., Bumbaširević, V. Z.,& Trajković, V. S.. (2012). Inhibition of AMPK-dependent autophagy enhances in vitro antiglioma effect of simvastatin. in Pharmacological Research, 65(1).
https://hdl.handle.net/21.15107/rcub_ibiss_1232

Misirkić Marjanović M, Janjetović K, Vučićević L, Tovilović-Kovačević G, Ristić BZ, Vilimanović U, Harhaji-Trajković L, Sumarac-Dumanović MS, Micić DD, Bumbaširević VZ, Trajković VS. Inhibition of AMPK-dependent autophagy enhances in vitro antiglioma effect of simvastatin. in Pharmacological Research. 2012;65(1):null-119.
https://hdl.handle.net/21.15107/rcub_ibiss_1232 .

Misirkić Marjanović, Maja, Janjetović, Kristina, Vučićević, Ljubica, Tovilović-Kovačević, Gordana, Ristić, Biljana Z, Vilimanović, Uros, Harhaji-Trajković, Ljubica, Sumarac-Dumanović, Mirjana S, Micić, Dragan D, Bumbaširević, Vladimir Z, Trajković, Vladimir S, "Inhibition of AMPK-dependent autophagy enhances in vitro antiglioma effect of simvastatin" in Pharmacological Research, 65, no. 1 (2012),
https://hdl.handle.net/21.15107/rcub_ibiss_1232 .