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  - 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  - 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 . .