TY  - CONF
AU  - Zeković, Janko
AU  - Vidičević Novaković, Sašenka
AU  - Tasić, Jelena
AU  - Stanojević, Željka
AU  - Milovanović, Andona
AU  - Tomonjić, Nina
AU  - Petričević, Saša
AU  - Zogović, Nevena
AU  - Tovilović-Kovačević, Gordana
AU  - Trajković, Vladimir
AU  - Isaković, Aleksandra
PY  - 2023
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5839
AB  - Introduction: Cuprizone is a copper chelating agent rensposible for toxic
demyelination. Although its mechanism of demyelination is not fully elucidated, its
toxicity is thought to result, at least partially, from induced autophagy.
The Aim: To examine the effect of cuprizone on autophagy markers in different
neural structures in rats with the assessment of behavior in the open field test.
Material and Methods: This study was performed on 16 female DA rats, 6 weeks
old.The control group (n=8) did not receive cuprizone, while the experimental group
(n=8) received food with 0.6% cuprizone content during 7 weeks. Afterwards,
locomotion and anxiety-like behavior were assessed in the open field test. Imunoblot
technique was performed on: cortex, corpus callosum, cerebellum and spinal cord, in
order to examine the markers of autophagy signaling pathway: pUlk, p62, Beclin1,
LC3II, pAMPK, pmTOR and pRaptor.
Results: Cuprizone-fed animals had a reduced locomotor activity and exhibited an
anxiety-like behavior. In the cortex, p62 and pAMPK were decreased, while pmTOR
tended to be lower. In the corpus callosum, pULK was increased and pmTOR was
decreased. LC3II tended to be increased, while pAMPK tended to be decreased. In the
cerebellum, pAMPK was reduced, while pmTOR was increased. In the spinal cord,
Beclin1 and pRaptor were decreased, while pmTOR, pAMPK, LC3II, p62 tended to
be decreased.
Conclusion: Long-term use of cuprizone leads to impaired locomotor activity and

anxiety-like behavior. Cuprizone-induced damage is most likely due to AMPK-
independent autophagy in the cortex and corpus callosum, while autophagy is

probably inhibited in the cerebellum and spinal cord.
PB  - Belgrade: Serbian Neuroscience Society
C3  - Book of abstracts: 8th Congress of Serbian Neuroscience Society with international participation; 2023 May 31 - Jun 2; Belgrade, Serbia
T1  - Effects of cuprizone-induced demyelination on autophagy markers in different neural structures with the evaluation of behavior in rats
SP  - 80
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5839
ER  - 

@conference{
author = "Zeković, Janko and Vidičević Novaković, Sašenka and Tasić, Jelena and Stanojević, Željka and Milovanović, Andona and Tomonjić, Nina and Petričević, Saša and Zogović, Nevena and Tovilović-Kovačević, Gordana and Trajković, Vladimir and Isaković, Aleksandra",
year = "2023",
abstract = "Introduction: Cuprizone is a copper chelating agent rensposible for toxic
demyelination. Although its mechanism of demyelination is not fully elucidated, its
toxicity is thought to result, at least partially, from induced autophagy.
The Aim: To examine the effect of cuprizone on autophagy markers in different
neural structures in rats with the assessment of behavior in the open field test.
Material and Methods: This study was performed on 16 female DA rats, 6 weeks
old.The control group (n=8) did not receive cuprizone, while the experimental group
(n=8) received food with 0.6% cuprizone content during 7 weeks. Afterwards,
locomotion and anxiety-like behavior were assessed in the open field test. Imunoblot
technique was performed on: cortex, corpus callosum, cerebellum and spinal cord, in
order to examine the markers of autophagy signaling pathway: pUlk, p62, Beclin1,
LC3II, pAMPK, pmTOR and pRaptor.
Results: Cuprizone-fed animals had a reduced locomotor activity and exhibited an
anxiety-like behavior. In the cortex, p62 and pAMPK were decreased, while pmTOR
tended to be lower. In the corpus callosum, pULK was increased and pmTOR was
decreased. LC3II tended to be increased, while pAMPK tended to be decreased. In the
cerebellum, pAMPK was reduced, while pmTOR was increased. In the spinal cord,
Beclin1 and pRaptor were decreased, while pmTOR, pAMPK, LC3II, p62 tended to
be decreased.
Conclusion: Long-term use of cuprizone leads to impaired locomotor activity and

anxiety-like behavior. Cuprizone-induced damage is most likely due to AMPK-
independent autophagy in the cortex and corpus callosum, while autophagy is

probably inhibited in the cerebellum and spinal cord.",
publisher = "Belgrade: Serbian Neuroscience Society",
journal = "Book of abstracts: 8th Congress of Serbian Neuroscience Society with international participation; 2023 May 31 - Jun 2; Belgrade, Serbia",
title = "Effects of cuprizone-induced demyelination on autophagy markers in different neural structures with the evaluation of behavior in rats",
pages = "80",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5839"
}

Zeković, J., Vidičević Novaković, S., Tasić, J., Stanojević, Ž., Milovanović, A., Tomonjić, N., Petričević, S., Zogović, N., Tovilović-Kovačević, G., Trajković, V.,& Isaković, A.. (2023). Effects of cuprizone-induced demyelination on autophagy markers in different neural structures with the evaluation of behavior in rats. in Book of abstracts: 8th Congress of Serbian Neuroscience Society with international participation; 2023 May 31 - Jun 2; Belgrade, Serbia
Belgrade: Serbian Neuroscience Society., 80.
https://hdl.handle.net/21.15107/rcub_ibiss_5839

Zeković J, Vidičević Novaković S, Tasić J, Stanojević Ž, Milovanović A, Tomonjić N, Petričević S, Zogović N, Tovilović-Kovačević G, Trajković V, Isaković A. Effects of cuprizone-induced demyelination on autophagy markers in different neural structures with the evaluation of behavior in rats. in Book of abstracts: 8th Congress of Serbian Neuroscience Society with international participation; 2023 May 31 - Jun 2; Belgrade, Serbia. 2023;:80.
https://hdl.handle.net/21.15107/rcub_ibiss_5839 .

Zeković, Janko, Vidičević Novaković, Sašenka, Tasić, Jelena, Stanojević, Željka, Milovanović, Andona, Tomonjić, Nina, Petričević, Saša, Zogović, Nevena, Tovilović-Kovačević, Gordana, Trajković, Vladimir, Isaković, Aleksandra, "Effects of cuprizone-induced demyelination on autophagy markers in different neural structures with the evaluation of behavior in rats" in Book of abstracts: 8th Congress of Serbian Neuroscience Society with international participation; 2023 May 31 - Jun 2; Belgrade, Serbia (2023):80,
https://hdl.handle.net/21.15107/rcub_ibiss_5839 .

TY  - JOUR
AU  - Vučićević, Ljubica
AU  - Misirkić Marjanović, Maja
AU  - Ćirić, Darko
AU  - Martinović, Tamara
AU  - Jovanović, Maja
AU  - Isaković, Aleksandra
AU  - Marković, Ivanka
AU  - Šaponjić, Jasna
AU  - Foretz, Marc
AU  - Rabanal-Ruiz, Yoana
AU  - Korolchuk, Viktor I.
AU  - Trajković, Vladimir
PY  - 2020
UR  - http://link.springer.com/10.1007/s00018-019-03356-2
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3528
AB  - We investigated the role of autophagy, a controlled lysosomal degradation of cellular macromolecules and organelles, in glutamate excitotoxicity during nutrient deprivation in vitro. The incubation in low-glucose serum/amino acid-free cell culture medium synergized with glutamate in increasing AMP/ATP ratio and causing excitotoxic necrosis in SH-SY5Y human neuroblastoma cells. Glutamate suppressed starvation-triggered autophagy, as confirmed by diminished intracellular acidification, lower LC3 punctuation and LC3-I conversion to autophagosome-associated LC3-II, reduced expression of proautophagic beclin-1 and ATG5, increase of the selective autophagic target NBR1, and decreased number of autophagic vesicles. Similar results were observed in PC12 rat pheochromocytoma cells. Both glutamate-mediated excitotoxicity and autophagy inhibition in starved SH-SY5Y cells were reverted by NMDA antagonist memantine and mimicked by NMDA agonists D-aspartate and ibotenate. Glutamate reduced starvation-triggered phosphorylation of the energy sensor AMP-activated protein kinase (AMPK) without affecting the activity of mammalian target of rapamycin complex 1, a major negative regulator of autophagy. This was associated with reduced mRNA levels of autophagy transcriptional activators (FOXO3, ATF4) and molecules involved in autophagy initiation (ULK1, ATG13, FIP200), autophagosome nucleation/elongation (ATG14, beclin-1, ATG5), and autophagic cargo delivery to autophagosomes (SQSTM1). Glutamate-mediated transcriptional repression of autophagy was alleviated by overexpression of constitutively active AMPK. Genetic or pharmacological AMPK activation by AMPK overexpression or metformin, as well as genetic or pharmacological autophagy induction by TFEB overexpression or lithium chloride, reduced the sensitivity of nutrient-deprived SH-SY5Y cells to glutamate excitotoxicity. These data indicate that transcriptional inhibition of AMPK-dependent cytoprotective autophagy is involved in glutamate-mediated excitotoxicity during nutrient deprivation in vitro.
T2  - Cellular and Molecular Life Sciences
T1  - Transcriptional block of AMPK-induced autophagy promotes glutamate excitotoxicity in nutrient-deprived SH-SY5Y neuroblastoma cells.
VL  - 77
DO  - 10.1007/s00018-019-03356-2
SP  - 3383
EP  - 3399
ER  - 

@article{
author = "Vučićević, Ljubica and Misirkić Marjanović, Maja and Ćirić, Darko and Martinović, Tamara and Jovanović, Maja and Isaković, Aleksandra and Marković, Ivanka and Šaponjić, Jasna and Foretz, Marc and Rabanal-Ruiz, Yoana and Korolchuk, Viktor I. and Trajković, Vladimir",
year = "2020",
abstract = "We investigated the role of autophagy, a controlled lysosomal degradation of cellular macromolecules and organelles, in glutamate excitotoxicity during nutrient deprivation in vitro. The incubation in low-glucose serum/amino acid-free cell culture medium synergized with glutamate in increasing AMP/ATP ratio and causing excitotoxic necrosis in SH-SY5Y human neuroblastoma cells. Glutamate suppressed starvation-triggered autophagy, as confirmed by diminished intracellular acidification, lower LC3 punctuation and LC3-I conversion to autophagosome-associated LC3-II, reduced expression of proautophagic beclin-1 and ATG5, increase of the selective autophagic target NBR1, and decreased number of autophagic vesicles. Similar results were observed in PC12 rat pheochromocytoma cells. Both glutamate-mediated excitotoxicity and autophagy inhibition in starved SH-SY5Y cells were reverted by NMDA antagonist memantine and mimicked by NMDA agonists D-aspartate and ibotenate. Glutamate reduced starvation-triggered phosphorylation of the energy sensor AMP-activated protein kinase (AMPK) without affecting the activity of mammalian target of rapamycin complex 1, a major negative regulator of autophagy. This was associated with reduced mRNA levels of autophagy transcriptional activators (FOXO3, ATF4) and molecules involved in autophagy initiation (ULK1, ATG13, FIP200), autophagosome nucleation/elongation (ATG14, beclin-1, ATG5), and autophagic cargo delivery to autophagosomes (SQSTM1). Glutamate-mediated transcriptional repression of autophagy was alleviated by overexpression of constitutively active AMPK. Genetic or pharmacological AMPK activation by AMPK overexpression or metformin, as well as genetic or pharmacological autophagy induction by TFEB overexpression or lithium chloride, reduced the sensitivity of nutrient-deprived SH-SY5Y cells to glutamate excitotoxicity. These data indicate that transcriptional inhibition of AMPK-dependent cytoprotective autophagy is involved in glutamate-mediated excitotoxicity during nutrient deprivation in vitro.",
journal = "Cellular and Molecular Life Sciences",
title = "Transcriptional block of AMPK-induced autophagy promotes glutamate excitotoxicity in nutrient-deprived SH-SY5Y neuroblastoma cells.",
volume = "77",
doi = "10.1007/s00018-019-03356-2",
pages = "3383-3399"
}

Vučićević, L., Misirkić Marjanović, M., Ćirić, D., Martinović, T., Jovanović, M., Isaković, A., Marković, I., Šaponjić, J., Foretz, M., Rabanal-Ruiz, Y., Korolchuk, V. I.,& Trajković, V.. (2020). Transcriptional block of AMPK-induced autophagy promotes glutamate excitotoxicity in nutrient-deprived SH-SY5Y neuroblastoma cells.. in Cellular and Molecular Life Sciences, 77, 3383-3399.
https://doi.org/10.1007/s00018-019-03356-2

Vučićević L, Misirkić Marjanović M, Ćirić D, Martinović T, Jovanović M, Isaković A, Marković I, Šaponjić J, Foretz M, Rabanal-Ruiz Y, Korolchuk VI, Trajković V. Transcriptional block of AMPK-induced autophagy promotes glutamate excitotoxicity in nutrient-deprived SH-SY5Y neuroblastoma cells.. in Cellular and Molecular Life Sciences. 2020;77:3383-3399.
doi:10.1007/s00018-019-03356-2 .

Vučićević, Ljubica, Misirkić Marjanović, Maja, Ćirić, Darko, Martinović, Tamara, Jovanović, Maja, Isaković, Aleksandra, Marković, Ivanka, Šaponjić, Jasna, Foretz, Marc, Rabanal-Ruiz, Yoana, Korolchuk, Viktor I., Trajković, Vladimir, "Transcriptional block of AMPK-induced autophagy promotes glutamate excitotoxicity in nutrient-deprived SH-SY5Y neuroblastoma cells." in Cellular and Molecular Life Sciences, 77 (2020):3383-3399,
https://doi.org/10.1007/s00018-019-03356-2 . .

TY  - CONF
AU  - Vučićević, Ljubica
AU  - Misirkić Marjanović, Maja
AU  - Ćirić, Darko
AU  - Martinović, Tamara
AU  - Jovanović, Maja
AU  - Isaković, Aleksandra
AU  - Marković, Ivanka
AU  - Zogović, Nevena
AU  - Foretz, Mark
AU  - Rabanal-Ruiz, Yoana
AU  - Korolchuk, Viktor
AU  - Trajković, Vladimir
PY  - 2019
UR  - https://www.fens.org/news-activities/fens-and-societies-calendar/meeting-event/fens-regional-meeting-2019
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6357
AB  - We investigated the effect of excitotoxic glutamate on nutrient starvation-induced autophagy, a process of lysosome-mediated degradation of cellular macromolecules and organelles. Incubation of SH-SY5Y human neuroblastoma cell line in glucose/amino acid/serum-free Hank Balanced Salt solution synergized with glutamate in causing energy stress and excitotoxic necrosis. Glutamate inhibited starvation-induced autophagy, as demonstrated by decreased intracellular acidification, lower LC3 punctuation, reduced conversion of LC3-I to LC3-II, reduced expression of autophagy activators beclin-1 and ATG5, increased
levels of the selective autophagic target NBR1, and decline in the number of autophagic vesicles observed by transmission electron microscopy. NMDA antagonist memantine restored LC3B-II accumulation in starved cells exposed to glutamate, indicating that glutamate exerts its inhibitory role on autophagy by activating NMDA receptors. The modulation of mTOR, the negative regulator of autophagy, was not responsible for glutamate-mediated autophagy inhibition during starvation. On the other hand, glutamate downregulated starvation-induced activation of the intracellular energy sensor AMP-activated protein
kinase (AMPK). This was associated with reduced mRNA expression of autophagy transcription factors FOXO3 and ATF4, as well as molecules involved in autophagy process (ULK1, ATG13, FIP200, ATG14, beclin-1, ATG5, ATG12, SQSTM1). The ability of glutamate to repress transcription of autophagy genes in starved cells was partly mediated by AMPK downregulation. Genetic or pharmacological AMPK activation by AMPK overexpression or metformin, as well as genetic or pharmacological autophagy induction by TFEB overexpression or lithium chloride, rescued cells from glutamate-mediated excitoxicity. These data indicate that transcriptional inhibition of AMPK-dependent autophagy is involved in glutamate-mediated excitotoxicity during nutrient deprivation in vitro.
PB  - Belgrade : Serbian Neuroscience Society
C3  - Book of Abstract: Federation of European Neuroscience Societies (FENS) Regional Meeting; 2019 Jul 10-13; Belgrade, Serbia
T1  - Autophagy regulation and its role in glutamate excitotoxicity during nutrient stress
SP  - 144
EP  - 144
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_6357
ER  - 

@conference{
author = "Vučićević, Ljubica and Misirkić Marjanović, Maja and Ćirić, Darko and Martinović, Tamara and Jovanović, Maja and Isaković, Aleksandra and Marković, Ivanka and Zogović, Nevena and Foretz, Mark and Rabanal-Ruiz, Yoana and Korolchuk, Viktor and Trajković, Vladimir",
year = "2019",
abstract = "We investigated the effect of excitotoxic glutamate on nutrient starvation-induced autophagy, a process of lysosome-mediated degradation of cellular macromolecules and organelles. Incubation of SH-SY5Y human neuroblastoma cell line in glucose/amino acid/serum-free Hank Balanced Salt solution synergized with glutamate in causing energy stress and excitotoxic necrosis. Glutamate inhibited starvation-induced autophagy, as demonstrated by decreased intracellular acidification, lower LC3 punctuation, reduced conversion of LC3-I to LC3-II, reduced expression of autophagy activators beclin-1 and ATG5, increased
levels of the selective autophagic target NBR1, and decline in the number of autophagic vesicles observed by transmission electron microscopy. NMDA antagonist memantine restored LC3B-II accumulation in starved cells exposed to glutamate, indicating that glutamate exerts its inhibitory role on autophagy by activating NMDA receptors. The modulation of mTOR, the negative regulator of autophagy, was not responsible for glutamate-mediated autophagy inhibition during starvation. On the other hand, glutamate downregulated starvation-induced activation of the intracellular energy sensor AMP-activated protein
kinase (AMPK). This was associated with reduced mRNA expression of autophagy transcription factors FOXO3 and ATF4, as well as molecules involved in autophagy process (ULK1, ATG13, FIP200, ATG14, beclin-1, ATG5, ATG12, SQSTM1). The ability of glutamate to repress transcription of autophagy genes in starved cells was partly mediated by AMPK downregulation. Genetic or pharmacological AMPK activation by AMPK overexpression or metformin, as well as genetic or pharmacological autophagy induction by TFEB overexpression or lithium chloride, rescued cells from glutamate-mediated excitoxicity. These data indicate that transcriptional inhibition of AMPK-dependent autophagy is involved in glutamate-mediated excitotoxicity during nutrient deprivation in vitro.",
publisher = "Belgrade : Serbian Neuroscience Society",
journal = "Book of Abstract: Federation of European Neuroscience Societies (FENS) Regional Meeting; 2019 Jul 10-13; Belgrade, Serbia",
title = "Autophagy regulation and its role in glutamate excitotoxicity during nutrient stress",
pages = "144-144",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_6357"
}

Vučićević, L., Misirkić Marjanović, M., Ćirić, D., Martinović, T., Jovanović, M., Isaković, A., Marković, I., Zogović, N., Foretz, M., Rabanal-Ruiz, Y., Korolchuk, V.,& Trajković, V.. (2019). Autophagy regulation and its role in glutamate excitotoxicity during nutrient stress. in Book of Abstract: Federation of European Neuroscience Societies (FENS) Regional Meeting; 2019 Jul 10-13; Belgrade, Serbia
Belgrade : Serbian Neuroscience Society., 144-144.
https://hdl.handle.net/21.15107/rcub_ibiss_6357

Vučićević L, Misirkić Marjanović M, Ćirić D, Martinović T, Jovanović M, Isaković A, Marković I, Zogović N, Foretz M, Rabanal-Ruiz Y, Korolchuk V, Trajković V. Autophagy regulation and its role in glutamate excitotoxicity during nutrient stress. in Book of Abstract: Federation of European Neuroscience Societies (FENS) Regional Meeting; 2019 Jul 10-13; Belgrade, Serbia. 2019;:144-144.
https://hdl.handle.net/21.15107/rcub_ibiss_6357 .

Vučićević, Ljubica, Misirkić Marjanović, Maja, Ćirić, Darko, Martinović, Tamara, Jovanović, Maja, Isaković, Aleksandra, Marković, Ivanka, Zogović, Nevena, Foretz, Mark, Rabanal-Ruiz, Yoana, Korolchuk, Viktor, Trajković, Vladimir, "Autophagy regulation and its role in glutamate excitotoxicity during nutrient stress" in Book of Abstract: Federation of European Neuroscience Societies (FENS) Regional Meeting; 2019 Jul 10-13; Belgrade, Serbia (2019):144-144,
https://hdl.handle.net/21.15107/rcub_ibiss_6357 .

TY  - JOUR
AU  - Pantović, Aleksandar
AU  - Bošnjak, Mihajlo
AU  - Arsikin, Katarina
AU  - Kosić, Milica
AU  - Mandić, Miloš
AU  - Ristić, Biljana
AU  - Tošić, Jelena
AU  - Grujičić, Danica
AU  - Isaković, Aleksandra
AU  - Micic, Nikola
AU  - Trajković, Vladimir
AU  - Harhaji-Trajković, Ljubica
PY  - 2017
UR  - http://linkinghub.elsevier.com/retrieve/pii/S1357272516303946
UR  - https://www.scopus.com/record/display.uri?eid=2-s2.0-85008690027&origin=SingleRecordEmailAlert&dgcid=scalert_sc_search_email&txGid=BCBFF82A73D51FA0ED62BC41FE5E5987.wsnAw8kcdt7IPYLO0V48gA%3A29
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/2512
AB  - We investigated the role of the intracellular energy-sensing AMP-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) pathway in the in vitro antiglioma effect of the cyclooxygenase (COX) inhibitor indomethacin. Indomethacin was more potent than COX inhibitors diclofenac, naproxen, and ketoprofen in reducing the viability of U251 human glioma cells. Antiglioma effect of the drug was associated with p21 increase and G2M cell cycle arrest, as well as with oxidative stress, mitochondrial depolarization, caspase activation, and the induction of apoptosis. Indomethacin increased the phosphorylation of AMPK and its targets Raptor and acetyl-CoA carboxylase (ACC), and reduced the phosphorylation of mTOR and mTOR complex 1 (mTORC1) substrates p70S6 kinase and PRAS40 (Ser183). AMPK knockdown by RNA interference, as well as the treatment with the mTORC1 activator leucine, prevented indomethacin-mediated mTORC1 inhibition and cytotoxic action, while AMPK activators metformin and AICAR mimicked the effects of the drug. AMPK activation by indomethacin correlated with intracellular ATP depletion and increase in AMP/ATP ratio, and was apparently independent of COX inhibition or the increase in intracellular calcium. Finally, the toxicity of indomethacin towards primary human glioma cells was associated with the activation of AMPK/Raptor/ACC and subsequent suppression of mTORC1/S6K. By demonstrating the involvement of AMPK/mTORC1 pathway in the antiglioma action of indomethacin, our results support its further exploration in glioma therapy.
T2  - The International Journal of Biochemistry & Cell Biology
T1  - In vitro antiglioma action of indomethacin is mediated via AMP-activated protein kinase/mTOR complex 1 signalling pathway
VL  - 83
DO  - 10.1016/j.biocel.2016.12.007
SP  - 84
EP  - 96
ER  - 

@article{
author = "Pantović, Aleksandar and Bošnjak, Mihajlo and Arsikin, Katarina and Kosić, Milica and Mandić, Miloš and Ristić, Biljana and Tošić, Jelena and Grujičić, Danica and Isaković, Aleksandra and Micic, Nikola and Trajković, Vladimir and Harhaji-Trajković, Ljubica",
year = "2017",
abstract = "We investigated the role of the intracellular energy-sensing AMP-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) pathway in the in vitro antiglioma effect of the cyclooxygenase (COX) inhibitor indomethacin. Indomethacin was more potent than COX inhibitors diclofenac, naproxen, and ketoprofen in reducing the viability of U251 human glioma cells. Antiglioma effect of the drug was associated with p21 increase and G2M cell cycle arrest, as well as with oxidative stress, mitochondrial depolarization, caspase activation, and the induction of apoptosis. Indomethacin increased the phosphorylation of AMPK and its targets Raptor and acetyl-CoA carboxylase (ACC), and reduced the phosphorylation of mTOR and mTOR complex 1 (mTORC1) substrates p70S6 kinase and PRAS40 (Ser183). AMPK knockdown by RNA interference, as well as the treatment with the mTORC1 activator leucine, prevented indomethacin-mediated mTORC1 inhibition and cytotoxic action, while AMPK activators metformin and AICAR mimicked the effects of the drug. AMPK activation by indomethacin correlated with intracellular ATP depletion and increase in AMP/ATP ratio, and was apparently independent of COX inhibition or the increase in intracellular calcium. Finally, the toxicity of indomethacin towards primary human glioma cells was associated with the activation of AMPK/Raptor/ACC and subsequent suppression of mTORC1/S6K. By demonstrating the involvement of AMPK/mTORC1 pathway in the antiglioma action of indomethacin, our results support its further exploration in glioma therapy.",
journal = "The International Journal of Biochemistry & Cell Biology",
title = "In vitro antiglioma action of indomethacin is mediated via AMP-activated protein kinase/mTOR complex 1 signalling pathway",
volume = "83",
doi = "10.1016/j.biocel.2016.12.007",
pages = "84-96"
}

Pantović, A., Bošnjak, M., Arsikin, K., Kosić, M., Mandić, M., Ristić, B., Tošić, J., Grujičić, D., Isaković, A., Micic, N., Trajković, V.,& Harhaji-Trajković, L.. (2017). In vitro antiglioma action of indomethacin is mediated via AMP-activated protein kinase/mTOR complex 1 signalling pathway. in The International Journal of Biochemistry & Cell Biology, 83, 84-96.
https://doi.org/10.1016/j.biocel.2016.12.007

Pantović A, Bošnjak M, Arsikin K, Kosić M, Mandić M, Ristić B, Tošić J, Grujičić D, Isaković A, Micic N, Trajković V, Harhaji-Trajković L. In vitro antiglioma action of indomethacin is mediated via AMP-activated protein kinase/mTOR complex 1 signalling pathway. in The International Journal of Biochemistry & Cell Biology. 2017;83:84-96.
doi:10.1016/j.biocel.2016.12.007 .

Pantović, Aleksandar, Bošnjak, Mihajlo, Arsikin, Katarina, Kosić, Milica, Mandić, Miloš, Ristić, Biljana, Tošić, Jelena, Grujičić, Danica, Isaković, Aleksandra, Micic, Nikola, Trajković, Vladimir, Harhaji-Trajković, Ljubica, "In vitro antiglioma action of indomethacin is mediated via AMP-activated protein kinase/mTOR complex 1 signalling pathway" in The International Journal of Biochemistry & Cell Biology, 83 (2017):84-96,
https://doi.org/10.1016/j.biocel.2016.12.007 . .

TY  - JOUR
AU  - Dinić, Jelena
AU  - Novaković, Miroslav
AU  - Podolski-Renić, Ana
AU  - Vajs, Vlatka
AU  - Tešević, Vele
AU  - Isaković, Aleksandra
AU  - Pešić, Milica
PY  - 2016
UR  - https://www.sciencedirect.com/science/article/pii/S0009279716300552
UR  - https://radar.ibiss.bg.ac.rs/123456789/3876
AB  - Diarylheptanoids represent a group of plant secondary metabolites that possess multiple biological properties and are increasingly recognized for their therapeutic potential. A comparative study was performed on structurally analogous diarylheptanoids isolated from the bark of green (Alnus viridis) and black alder (Alnus glutinosa) to address their biological effects and determine structure-activity relationship. The structures and configurations of all compounds were elucidated by NMR, HR-ESI-MS, UV and IR. Diarylheptanoids actions were studied in human non-small cell lung carcinoma cells (NCI-H460) and normal keratinocytes (HaCaT). A. viridis compounds 3v, 5v, 8v and 9v that possess a carbonyl group at C-3 were considerably more potent than compounds without this group. A. viridis/A. glutinosa analogue pairs, 5v/5g and 9v/9g, which differ in the presence of 3' and 3″-OH groups, were evaluated for anticancer activity and selectivity. 5v and 9v that do not possess 3' and 3″-OH groups showed significantly higher cytotoxicity compared to analogues 5g and 9g. In addition, these two A. viridis compounds induced a more prominent apoptosis in both cell lines and an increase in subG0 cell cycle phase, compared to their A. glutinosa analogues. 5v and 9v treatment triggered intracellular superoxide anion accumulation and notably decreased mitochondrial transmembrane potential. In HaCaT cells, 9v and 9g with a 4,5 double bond caused a more prominent loss of mitochondrial transmembrane potential compared to 5v and 5g which possess a 5-methoxy group instead. Although green alder diarylheptanoids 5v and 9v displayed higher cytotoxicity, their analogues from black alder 5g and 9g could be more favorable for therapeutic use since they were more active in cancer cells than in normal keratinocytes. These results indicate that minor differences in the chemical structure can greatly influence the effect of diarylheptanoids on apoptosis and redox status and determine their selectivity towards cancer cells.
PB  - Shannon : Elsevier
T2  - Chemico-Biological Interactions
T1  - Structural differences in diarylheptanoids analogues from Alnus viridis and Alnus glutinosa influence their activity and selectivity towards cancer cells
VL  - 249
DO  - 10.1016/j.cbi.2016.02.019
SP  - 36
EP  - 45
ER  - 

@article{
author = "Dinić, Jelena and Novaković, Miroslav and Podolski-Renić, Ana and Vajs, Vlatka and Tešević, Vele and Isaković, Aleksandra and Pešić, Milica",
year = "2016",
abstract = "Diarylheptanoids represent a group of plant secondary metabolites that possess multiple biological properties and are increasingly recognized for their therapeutic potential. A comparative study was performed on structurally analogous diarylheptanoids isolated from the bark of green (Alnus viridis) and black alder (Alnus glutinosa) to address their biological effects and determine structure-activity relationship. The structures and configurations of all compounds were elucidated by NMR, HR-ESI-MS, UV and IR. Diarylheptanoids actions were studied in human non-small cell lung carcinoma cells (NCI-H460) and normal keratinocytes (HaCaT). A. viridis compounds 3v, 5v, 8v and 9v that possess a carbonyl group at C-3 were considerably more potent than compounds without this group. A. viridis/A. glutinosa analogue pairs, 5v/5g and 9v/9g, which differ in the presence of 3' and 3″-OH groups, were evaluated for anticancer activity and selectivity. 5v and 9v that do not possess 3' and 3″-OH groups showed significantly higher cytotoxicity compared to analogues 5g and 9g. In addition, these two A. viridis compounds induced a more prominent apoptosis in both cell lines and an increase in subG0 cell cycle phase, compared to their A. glutinosa analogues. 5v and 9v treatment triggered intracellular superoxide anion accumulation and notably decreased mitochondrial transmembrane potential. In HaCaT cells, 9v and 9g with a 4,5 double bond caused a more prominent loss of mitochondrial transmembrane potential compared to 5v and 5g which possess a 5-methoxy group instead. Although green alder diarylheptanoids 5v and 9v displayed higher cytotoxicity, their analogues from black alder 5g and 9g could be more favorable for therapeutic use since they were more active in cancer cells than in normal keratinocytes. These results indicate that minor differences in the chemical structure can greatly influence the effect of diarylheptanoids on apoptosis and redox status and determine their selectivity towards cancer cells.",
publisher = "Shannon : Elsevier",
journal = "Chemico-Biological Interactions",
title = "Structural differences in diarylheptanoids analogues from Alnus viridis and Alnus glutinosa influence their activity and selectivity towards cancer cells",
volume = "249",
doi = "10.1016/j.cbi.2016.02.019",
pages = "36-45"
}

Dinić, J., Novaković, M., Podolski-Renić, A., Vajs, V., Tešević, V., Isaković, A.,& Pešić, M.. (2016). Structural differences in diarylheptanoids analogues from Alnus viridis and Alnus glutinosa influence their activity and selectivity towards cancer cells. in Chemico-Biological Interactions
Shannon : Elsevier., 249, 36-45.
https://doi.org/10.1016/j.cbi.2016.02.019

Dinić J, Novaković M, Podolski-Renić A, Vajs V, Tešević V, Isaković A, Pešić M. Structural differences in diarylheptanoids analogues from Alnus viridis and Alnus glutinosa influence their activity and selectivity towards cancer cells. in Chemico-Biological Interactions. 2016;249:36-45.
doi:10.1016/j.cbi.2016.02.019 .

Dinić, Jelena, Novaković, Miroslav, Podolski-Renić, Ana, Vajs, Vlatka, Tešević, Vele, Isaković, Aleksandra, Pešić, Milica, "Structural differences in diarylheptanoids analogues from Alnus viridis and Alnus glutinosa influence their activity and selectivity towards cancer cells" in Chemico-Biological Interactions, 249 (2016):36-45,
https://doi.org/10.1016/j.cbi.2016.02.019 . .

TY  - JOUR
AU  - Dinić, Jelena
AU  - Novaković, Miroslav
AU  - Podolski-Renić, Ana
AU  - Vajs, Vlatka
AU  - Tešević, Vele
AU  - Isaković, Aleksandra
AU  - Pešić, Milica
PY  - 2016
UR  - http://www.scopus.com/inward/record.url?eid=2-s2.0-84960351174&partnerID=tZOtx3y1
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/2535
AB  - Diarylheptanoids represent a group of plant secondary metabolites that possess multiple biological properties and are increasingly recognized for their therapeutic potential. A comparative study was performed on structurally analogous diarylheptanoids isolated from the bark of green (Alnus viridis) and black alder (Alnus glutinosa) to address their biological effects and determine structure-activity relationship. The structures and configurations of all compounds were elucidated by NMR, HR-ESI-MS, UV and IR. Diarylheptanoids actions were studied in human non-small cell lung carcinoma cells (NCI-H460) and normal keratinocytes (HaCaT). A. viridis compounds 3v, 5v, 8v and 9v that possess a carbonyl group at C-3 were considerably more potent than compounds without this group. A. viridis/A. glutinosa analogue pairs, 5v/5g and 9v/9g, which differ in the presence of 3' and 3″-OH groups, were evaluated for anticancer activity and selectivity. 5v and 9v that do not possess 3' and 3″-OH groups showed significantly higher cytotoxicity compared to analogues 5g and 9g. In addition, these two A. viridis compounds induced a more prominent apoptosis in both cell lines and an increase in subG0 cell cycle phase, compared to their A. glutinosa analogues. 5v and 9v treatment triggered intracellular superoxide anion accumulation and notably decreased mitochondrial transmembrane potential. In HaCaT cells, 9v and 9g with a 4,5 double bond caused a more prominent loss of mitochondrial transmembrane potential compared to 5v and 5g which possess a 5-methoxy group instead. Although green alder diarylheptanoids 5v and 9v displayed higher cytotoxicity, their analogues from black alder 5g and 9g could be more favorable for therapeutic use since they were more active in cancer cells than in normal keratinocytes. These results indicate that minor differences in the chemical structure can greatly influence the effect of diarylheptanoids on apoptosis and redox status and determine their selectivity towards cancer cells.
T2  - Chemico-Biological Interactions
T1  - Structural differences in diarylheptanoids analogues from Alnus viridis and Alnus glutinosa influence their activity and selectivity towards cancer cells.
VL  - 249
DO  - 10.1016/j.cbi.2016.02.019
SP  - 36
EP  - 45
ER  - 

@article{
author = "Dinić, Jelena and Novaković, Miroslav and Podolski-Renić, Ana and Vajs, Vlatka and Tešević, Vele and Isaković, Aleksandra and Pešić, Milica",
year = "2016",
abstract = "Diarylheptanoids represent a group of plant secondary metabolites that possess multiple biological properties and are increasingly recognized for their therapeutic potential. A comparative study was performed on structurally analogous diarylheptanoids isolated from the bark of green (Alnus viridis) and black alder (Alnus glutinosa) to address their biological effects and determine structure-activity relationship. The structures and configurations of all compounds were elucidated by NMR, HR-ESI-MS, UV and IR. Diarylheptanoids actions were studied in human non-small cell lung carcinoma cells (NCI-H460) and normal keratinocytes (HaCaT). A. viridis compounds 3v, 5v, 8v and 9v that possess a carbonyl group at C-3 were considerably more potent than compounds without this group. A. viridis/A. glutinosa analogue pairs, 5v/5g and 9v/9g, which differ in the presence of 3' and 3″-OH groups, were evaluated for anticancer activity and selectivity. 5v and 9v that do not possess 3' and 3″-OH groups showed significantly higher cytotoxicity compared to analogues 5g and 9g. In addition, these two A. viridis compounds induced a more prominent apoptosis in both cell lines and an increase in subG0 cell cycle phase, compared to their A. glutinosa analogues. 5v and 9v treatment triggered intracellular superoxide anion accumulation and notably decreased mitochondrial transmembrane potential. In HaCaT cells, 9v and 9g with a 4,5 double bond caused a more prominent loss of mitochondrial transmembrane potential compared to 5v and 5g which possess a 5-methoxy group instead. Although green alder diarylheptanoids 5v and 9v displayed higher cytotoxicity, their analogues from black alder 5g and 9g could be more favorable for therapeutic use since they were more active in cancer cells than in normal keratinocytes. These results indicate that minor differences in the chemical structure can greatly influence the effect of diarylheptanoids on apoptosis and redox status and determine their selectivity towards cancer cells.",
journal = "Chemico-Biological Interactions",
title = "Structural differences in diarylheptanoids analogues from Alnus viridis and Alnus glutinosa influence their activity and selectivity towards cancer cells.",
volume = "249",
doi = "10.1016/j.cbi.2016.02.019",
pages = "36-45"
}

Dinić, J., Novaković, M., Podolski-Renić, A., Vajs, V., Tešević, V., Isaković, A.,& Pešić, M.. (2016). Structural differences in diarylheptanoids analogues from Alnus viridis and Alnus glutinosa influence their activity and selectivity towards cancer cells.. in Chemico-Biological Interactions, 249, 36-45.
https://doi.org/10.1016/j.cbi.2016.02.019

Dinić J, Novaković M, Podolski-Renić A, Vajs V, Tešević V, Isaković A, Pešić M. Structural differences in diarylheptanoids analogues from Alnus viridis and Alnus glutinosa influence their activity and selectivity towards cancer cells.. in Chemico-Biological Interactions. 2016;249:36-45.
doi:10.1016/j.cbi.2016.02.019 .

Dinić, Jelena, Novaković, Miroslav, Podolski-Renić, Ana, Vajs, Vlatka, Tešević, Vele, Isaković, Aleksandra, Pešić, Milica, "Structural differences in diarylheptanoids analogues from Alnus viridis and Alnus glutinosa influence their activity and selectivity towards cancer cells." in Chemico-Biological Interactions, 249 (2016):36-45,
https://doi.org/10.1016/j.cbi.2016.02.019 . .

TY  - JOUR
AU  - Dinić, Jelena
AU  - Ranđelović, Teodora
AU  - Stanković, Tijana
AU  - Dragoj, Miodrag
AU  - Isaković, Aleksandra
AU  - Novaković, Miroslav
AU  - Pešić, Milica
PY  - 2015
UR  - https://www.sciencedirect.com/science/article/abs/pii/S0367326X1530040X
UR  - https://radar.ibiss.bg.ac.rs/123456789/3865
AB  - Medicinal plants are recognized from ancient times as a source of diverse therapeutic agents and many of them are used as dietary supplements. Comprehensive approaches are needed that would identify bioactive components with evident activity against specific indications and provide a better link between science (ethno-botany, chemistry, biology and pharmacology) and market. Recently, the bark of black alder (Alnus glutinosa) appeared at market in the form of food supplement for treatment of different skin conditions. This study aimed to evaluate protective effects of two diarylheptanoids isolated from the bark of black alder: platyphylloside, 5(S)-1,7-di(4-hydroxyphenyl)-3-heptanone-5-O-β-D-glucopyranoside (1) and its newly discovered analog 5(S)-1,7-di(4-hydroxyphenyl)-5-O-β-D-[6-(E-p-coumaroylglucopyranosyl)]heptane-3-one (2) towards doxorubicin damaging activity. To that end, we employed HaCaT cells, non-cancerous human keratinocytes commonly used for skin regenerative studies. Diarylheptanoids significantly antagonized the effects of doxorubicin by lowering the sensitivity of HaCaT cells to this drug. Compound 2 prevented doxorubicin-induced cell death by activating autophagy. Both 1 and 2 protected HaCaT cells against doxorubicin-induced DNA damage. They significantly promoted migration and affected F-actin distribution. These results indicate that chemo-protective effects of diarylheptanoids may occur at multiple subcellular levels. Therefore, diarylheptanoids 1 and 2 could be considered as protective agents for non-cancerous dividing cells during chemotherapy.
PB  - Elsevier
T2  - Fitoterapia
T1  - Chemo-protective and regenerative effects of diarylheptanoids from the bark of black alder (Alnus glutinosa) in human normal keratinocytes
VL  - 105
DO  - 10.1016/j.fitote.2015.07.003
SP  - 169
EP  - 176
ER  - 

@article{
author = "Dinić, Jelena and Ranđelović, Teodora and Stanković, Tijana and Dragoj, Miodrag and Isaković, Aleksandra and Novaković, Miroslav and Pešić, Milica",
year = "2015",
abstract = "Medicinal plants are recognized from ancient times as a source of diverse therapeutic agents and many of them are used as dietary supplements. Comprehensive approaches are needed that would identify bioactive components with evident activity against specific indications and provide a better link between science (ethno-botany, chemistry, biology and pharmacology) and market. Recently, the bark of black alder (Alnus glutinosa) appeared at market in the form of food supplement for treatment of different skin conditions. This study aimed to evaluate protective effects of two diarylheptanoids isolated from the bark of black alder: platyphylloside, 5(S)-1,7-di(4-hydroxyphenyl)-3-heptanone-5-O-β-D-glucopyranoside (1) and its newly discovered analog 5(S)-1,7-di(4-hydroxyphenyl)-5-O-β-D-[6-(E-p-coumaroylglucopyranosyl)]heptane-3-one (2) towards doxorubicin damaging activity. To that end, we employed HaCaT cells, non-cancerous human keratinocytes commonly used for skin regenerative studies. Diarylheptanoids significantly antagonized the effects of doxorubicin by lowering the sensitivity of HaCaT cells to this drug. Compound 2 prevented doxorubicin-induced cell death by activating autophagy. Both 1 and 2 protected HaCaT cells against doxorubicin-induced DNA damage. They significantly promoted migration and affected F-actin distribution. These results indicate that chemo-protective effects of diarylheptanoids may occur at multiple subcellular levels. Therefore, diarylheptanoids 1 and 2 could be considered as protective agents for non-cancerous dividing cells during chemotherapy.",
publisher = "Elsevier",
journal = "Fitoterapia",
title = "Chemo-protective and regenerative effects of diarylheptanoids from the bark of black alder (Alnus glutinosa) in human normal keratinocytes",
volume = "105",
doi = "10.1016/j.fitote.2015.07.003",
pages = "169-176"
}

Dinić, J., Ranđelović, T., Stanković, T., Dragoj, M., Isaković, A., Novaković, M.,& Pešić, M.. (2015). Chemo-protective and regenerative effects of diarylheptanoids from the bark of black alder (Alnus glutinosa) in human normal keratinocytes. in Fitoterapia
Elsevier., 105, 169-176.
https://doi.org/10.1016/j.fitote.2015.07.003

Dinić J, Ranđelović T, Stanković T, Dragoj M, Isaković A, Novaković M, Pešić M. Chemo-protective and regenerative effects of diarylheptanoids from the bark of black alder (Alnus glutinosa) in human normal keratinocytes. in Fitoterapia. 2015;105:169-176.
doi:10.1016/j.fitote.2015.07.003 .

Dinić, Jelena, Ranđelović, Teodora, Stanković, Tijana, Dragoj, Miodrag, Isaković, Aleksandra, Novaković, Miroslav, Pešić, Milica, "Chemo-protective and regenerative effects of diarylheptanoids from the bark of black alder (Alnus glutinosa) in human normal keratinocytes" in Fitoterapia, 105 (2015):169-176,
https://doi.org/10.1016/j.fitote.2015.07.003 . .

TY  - JOUR
AU  - Dinić, Jelena
AU  - Ranđelović, Teodora
AU  - Stanković, Tijana
AU  - Dragoj, Miodrag
AU  - Isaković, Aleksandra
AU  - Novaković, Miroslav
AU  - Pešić, Milica
PY  - 2015
UR  - https://www.sciencedirect.com/science/article/abs/pii/S0367326X1530040X
UR  - https://radar.ibiss.bg.ac.rs/123456789/3864
AB  - Medicinal plants are recognized from ancient times as a source of diverse therapeutic agents and many of them are used as dietary supplements. Comprehensive approaches are needed that would identify bioactive components with evident activity against specific indications and provide a better link between science (ethno-botany, chemistry, biology and pharmacology) and market. Recently, the bark of black alder (Alnus glutinosa) appeared at market in the form of food supplement for treatment of different skin conditions. This study aimed to evaluate protective effects of two diarylheptanoids isolated from the bark of black alder: platyphylloside, 5(S)-1,7-di(4-hydroxyphenyl)-3-heptanone-5-O-β-D-glucopyranoside (1) and its newly discovered analog 5(S)-1,7-di(4-hydroxyphenyl)-5-O-β-D-[6-(E-p-coumaroylglucopyranosyl)]heptane-3-one (2) towards doxorubicin damaging activity. To that end, we employed HaCaT cells, non-cancerous human keratinocytes commonly used for skin regenerative studies. Diarylheptanoids significantly antagonized the effects of doxorubicin by lowering the sensitivity of HaCaT cells to this drug. Compound 2 prevented doxorubicin-induced cell death by activating autophagy. Both 1 and 2 protected HaCaT cells against doxorubicin-induced DNA damage. They significantly promoted migration and affected F-actin distribution. These results indicate that chemo-protective effects of diarylheptanoids may occur at multiple subcellular levels. Therefore, diarylheptanoids 1 and 2 could be considered as protective agents for non-cancerous dividing cells during chemotherapy.
PB  - Elsevier
T2  - Fitoterapia
T1  - Chemo-protective and regenerative effects of diarylheptanoids from the bark of black alder (Alnus glutinosa) in human normal keratinocytes
VL  - 105
DO  - 10.1016/j.fitote.2015.07.003
SP  - 169
EP  - 176
ER  - 

@article{
author = "Dinić, Jelena and Ranđelović, Teodora and Stanković, Tijana and Dragoj, Miodrag and Isaković, Aleksandra and Novaković, Miroslav and Pešić, Milica",
year = "2015",
abstract = "Medicinal plants are recognized from ancient times as a source of diverse therapeutic agents and many of them are used as dietary supplements. Comprehensive approaches are needed that would identify bioactive components with evident activity against specific indications and provide a better link between science (ethno-botany, chemistry, biology and pharmacology) and market. Recently, the bark of black alder (Alnus glutinosa) appeared at market in the form of food supplement for treatment of different skin conditions. This study aimed to evaluate protective effects of two diarylheptanoids isolated from the bark of black alder: platyphylloside, 5(S)-1,7-di(4-hydroxyphenyl)-3-heptanone-5-O-β-D-glucopyranoside (1) and its newly discovered analog 5(S)-1,7-di(4-hydroxyphenyl)-5-O-β-D-[6-(E-p-coumaroylglucopyranosyl)]heptane-3-one (2) towards doxorubicin damaging activity. To that end, we employed HaCaT cells, non-cancerous human keratinocytes commonly used for skin regenerative studies. Diarylheptanoids significantly antagonized the effects of doxorubicin by lowering the sensitivity of HaCaT cells to this drug. Compound 2 prevented doxorubicin-induced cell death by activating autophagy. Both 1 and 2 protected HaCaT cells against doxorubicin-induced DNA damage. They significantly promoted migration and affected F-actin distribution. These results indicate that chemo-protective effects of diarylheptanoids may occur at multiple subcellular levels. Therefore, diarylheptanoids 1 and 2 could be considered as protective agents for non-cancerous dividing cells during chemotherapy.",
publisher = "Elsevier",
journal = "Fitoterapia",
title = "Chemo-protective and regenerative effects of diarylheptanoids from the bark of black alder (Alnus glutinosa) in human normal keratinocytes",
volume = "105",
doi = "10.1016/j.fitote.2015.07.003",
pages = "169-176"
}

Dinić, J., Ranđelović, T., Stanković, T., Dragoj, M., Isaković, A., Novaković, M.,& Pešić, M.. (2015). Chemo-protective and regenerative effects of diarylheptanoids from the bark of black alder (Alnus glutinosa) in human normal keratinocytes. in Fitoterapia
Elsevier., 105, 169-176.
https://doi.org/10.1016/j.fitote.2015.07.003

Dinić J, Ranđelović T, Stanković T, Dragoj M, Isaković A, Novaković M, Pešić M. Chemo-protective and regenerative effects of diarylheptanoids from the bark of black alder (Alnus glutinosa) in human normal keratinocytes. in Fitoterapia. 2015;105:169-176.
doi:10.1016/j.fitote.2015.07.003 .

Dinić, Jelena, Ranđelović, Teodora, Stanković, Tijana, Dragoj, Miodrag, Isaković, Aleksandra, Novaković, Miroslav, Pešić, Milica, "Chemo-protective and regenerative effects of diarylheptanoids from the bark of black alder (Alnus glutinosa) in human normal keratinocytes" in Fitoterapia, 105 (2015):169-176,
https://doi.org/10.1016/j.fitote.2015.07.003 . .

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  - Isaković, Aleksandra
AU  - Marković, Zoran
AU  - Todorović-Marković, Biljana
AU  - Nikolić, Nadežda
AU  - Vranješ-Đurić, Sanja
AU  - Mirković, Marija
AU  - Dramićanin, Miroslav
AU  - Harhaji-Trajković, Ljubica
AU  - Zogović, Nevena
AU  - Nikolić, Zoran
AU  - Trajković, Vladimir
PY  - 2006
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3589
AB  - The mechanisms underlying the cytotoxic action of pure fullerene suspension (nano-C 60 ) and water-soluble polyhydroxylated fullerene [C 60 (OH) n ] were investigated. Crystal violet assay for cell viability demonstrated that nano-C 60 was at least three orders of magnitude more toxic than C 60 (OH) n to mouse L929 fibrosarcoma, rat C6 glioma, and U251 human glioma cell lines. Flow cytometry analysis of cells stained with propidium iodide (PI), PI/annexin V-fluorescein isothiocyanate, or the redox-sensitive dye dihydrorhodamine revealed that nano-C 60 caused rapid (observable after few hours), reactive oxygen species (ROS)-associated necrosis characterized by cell membrane damage without DNA fragmentation. In contrast, C 60 (OH) n caused delayed, ROS-independent cell death with characteristics of apoptosis, including DNA fragmentation and loss of cell membrane asymmetry in the absence of increased permeability. Accordingly, the antioxidant N-acetylcysteine protected the cell lines from nano-C 60 toxicity, but not C 60 (OH) n toxicity, while the pan-caspase inhibitor z-VAD-fmk blocked C 60 (OH) n -induced apoptosis, but not nano-C 60 -mediated necrosis. Finally, C 60 (OH) n antagomozed, while nano-C 60 synergized with, the cytotoxic action of oxidative stress-inducing agents hydrogen peroxide and peroxynitrite donor 3-morpholinosydnonimine. Therefore, unlike polyhydroxylated C 60 that exerts mainly antioxidant/cytoprotective and only mild ROS-independent pro-apoptotic activity, pure crystalline C 60 seems to be endowed with strong pro-oxidant capacity responsible for the rapid necrotic cell death.
PB  - Oxford University Press (OUP)
T2  - Toxicological Sciences
T1  - Distinct Cytotoxic Mechanisms of Pristine versus Hydroxylated Fullerene
IS  - 1
VL  - 91
DO  - 10.1093/toxsci/kfj127
SP  - 173
EP  - 183
ER  - 

@article{
author = "Isaković, Aleksandra and Marković, Zoran and Todorović-Marković, Biljana and Nikolić, Nadežda and Vranješ-Đurić, Sanja and Mirković, Marija and Dramićanin, Miroslav and Harhaji-Trajković, Ljubica and Zogović, Nevena and Nikolić, Zoran and Trajković, Vladimir",
year = "2006",
abstract = "The mechanisms underlying the cytotoxic action of pure fullerene suspension (nano-C 60 ) and water-soluble polyhydroxylated fullerene [C 60 (OH) n ] were investigated. Crystal violet assay for cell viability demonstrated that nano-C 60 was at least three orders of magnitude more toxic than C 60 (OH) n to mouse L929 fibrosarcoma, rat C6 glioma, and U251 human glioma cell lines. Flow cytometry analysis of cells stained with propidium iodide (PI), PI/annexin V-fluorescein isothiocyanate, or the redox-sensitive dye dihydrorhodamine revealed that nano-C 60 caused rapid (observable after few hours), reactive oxygen species (ROS)-associated necrosis characterized by cell membrane damage without DNA fragmentation. In contrast, C 60 (OH) n caused delayed, ROS-independent cell death with characteristics of apoptosis, including DNA fragmentation and loss of cell membrane asymmetry in the absence of increased permeability. Accordingly, the antioxidant N-acetylcysteine protected the cell lines from nano-C 60 toxicity, but not C 60 (OH) n toxicity, while the pan-caspase inhibitor z-VAD-fmk blocked C 60 (OH) n -induced apoptosis, but not nano-C 60 -mediated necrosis. Finally, C 60 (OH) n antagomozed, while nano-C 60 synergized with, the cytotoxic action of oxidative stress-inducing agents hydrogen peroxide and peroxynitrite donor 3-morpholinosydnonimine. Therefore, unlike polyhydroxylated C 60 that exerts mainly antioxidant/cytoprotective and only mild ROS-independent pro-apoptotic activity, pure crystalline C 60 seems to be endowed with strong pro-oxidant capacity responsible for the rapid necrotic cell death.",
publisher = "Oxford University Press (OUP)",
journal = "Toxicological Sciences",
title = "Distinct Cytotoxic Mechanisms of Pristine versus Hydroxylated Fullerene",
number = "1",
volume = "91",
doi = "10.1093/toxsci/kfj127",
pages = "173-183"
}

Isaković, A., Marković, Z., Todorović-Marković, B., Nikolić, N., Vranješ-Đurić, S., Mirković, M., Dramićanin, M., Harhaji-Trajković, L., Zogović, N., Nikolić, Z.,& Trajković, V.. (2006). Distinct Cytotoxic Mechanisms of Pristine versus Hydroxylated Fullerene. in Toxicological Sciences
Oxford University Press (OUP)., 91(1), 173-183.
https://doi.org/10.1093/toxsci/kfj127

Isaković A, Marković Z, Todorović-Marković B, Nikolić N, Vranješ-Đurić S, Mirković M, Dramićanin M, Harhaji-Trajković L, Zogović N, Nikolić Z, Trajković V. Distinct Cytotoxic Mechanisms of Pristine versus Hydroxylated Fullerene. in Toxicological Sciences. 2006;91(1):173-183.
doi:10.1093/toxsci/kfj127 .

Isaković, Aleksandra, Marković, Zoran, Todorović-Marković, Biljana, Nikolić, Nadežda, Vranješ-Đurić, Sanja, Mirković, Marija, Dramićanin, Miroslav, Harhaji-Trajković, Ljubica, Zogović, Nevena, Nikolić, Zoran, Trajković, Vladimir, "Distinct Cytotoxic Mechanisms of Pristine versus Hydroxylated Fullerene" in Toxicological Sciences, 91, no. 1 (2006):173-183,
https://doi.org/10.1093/toxsci/kfj127 . .

TY  - JOUR
AU  - Harhaji-Trajković, Ljubica
AU  - Popadić, Dušan
AU  - Miljković, Đorđe
AU  - Stojanović, Ivana D.
AU  - Isaković, Aleksandra
AU  - Trajković, Vladimir
PY  - 2005
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6015
AB  - The influence of environmental pH on the production of tumoricidal free radical nitric oxide (NO) was investigated in mouse fibrosarcoma L929 and rat glioma C6 cell lines. A combination of IFN-gamma and IL-1 induced a significant NO release and subsequent reduction of cell viability in tumor cell lines. Acidification of cell culture medium reduced tumor cell NO production in a pH-dependent manner. While the inhibitory effect of acidosis on NO production in C6 cells was associated with a further decrease in cell viability, it completely rescued L929 cells from NO-dependent apoptotic and necrotic death. Acidic pH diminished IFN-gamma+ IL-1-induced expression of inducible NO synthase (iNOS) mRNA and protein, and abolished the activation of iNOS transcription factor IRF-1 in L929 cells. Moreover, extracellular acidosis significantly impaired cytokine-induced phosphorylation of MAP kinase p44/42 (ERK1/2) and subsequent expression of transcription factor c-Fos in L929 cells. Finally, mild acidosis (pH 6.8) augmented, while severe acidosis (pH 6.0) reduced, IFN-gamma-induced iNOS activation/NO release and NO-dependent anticancer activity of rat and mouse macrophages. Taken together, our findings indicate that modulation of macrophage and tumor cell iNOS by an acidic microenvironment might influence the progression of NO-sensitive solid tumors.
PB  - Elsevier Inc.
T2  - Free Radical Biology and Medicine
T1  - Acidosis affects tumor cell survival through modulation of nitric oxide release
IS  - 2
VL  - 40
DO  - 10.1016/j.freeradbiomed.2005.08.027
SP  - 226
EP  - 235
ER  - 

@article{
author = "Harhaji-Trajković, Ljubica and Popadić, Dušan and Miljković, Đorđe and Stojanović, Ivana D. and Isaković, Aleksandra and Trajković, Vladimir",
year = "2005",
abstract = "The influence of environmental pH on the production of tumoricidal free radical nitric oxide (NO) was investigated in mouse fibrosarcoma L929 and rat glioma C6 cell lines. A combination of IFN-gamma and IL-1 induced a significant NO release and subsequent reduction of cell viability in tumor cell lines. Acidification of cell culture medium reduced tumor cell NO production in a pH-dependent manner. While the inhibitory effect of acidosis on NO production in C6 cells was associated with a further decrease in cell viability, it completely rescued L929 cells from NO-dependent apoptotic and necrotic death. Acidic pH diminished IFN-gamma+ IL-1-induced expression of inducible NO synthase (iNOS) mRNA and protein, and abolished the activation of iNOS transcription factor IRF-1 in L929 cells. Moreover, extracellular acidosis significantly impaired cytokine-induced phosphorylation of MAP kinase p44/42 (ERK1/2) and subsequent expression of transcription factor c-Fos in L929 cells. Finally, mild acidosis (pH 6.8) augmented, while severe acidosis (pH 6.0) reduced, IFN-gamma-induced iNOS activation/NO release and NO-dependent anticancer activity of rat and mouse macrophages. Taken together, our findings indicate that modulation of macrophage and tumor cell iNOS by an acidic microenvironment might influence the progression of NO-sensitive solid tumors.",
publisher = "Elsevier Inc.",
journal = "Free Radical Biology and Medicine",
title = "Acidosis affects tumor cell survival through modulation of nitric oxide release",
number = "2",
volume = "40",
doi = "10.1016/j.freeradbiomed.2005.08.027",
pages = "226-235"
}

Harhaji-Trajković, L., Popadić, D., Miljković, Đ., Stojanović, I. D., Isaković, A.,& Trajković, V.. (2005). Acidosis affects tumor cell survival through modulation of nitric oxide release. in Free Radical Biology and Medicine
Elsevier Inc.., 40(2), 226-235.
https://doi.org/10.1016/j.freeradbiomed.2005.08.027

Harhaji-Trajković L, Popadić D, Miljković Đ, Stojanović ID, Isaković A, Trajković V. Acidosis affects tumor cell survival through modulation of nitric oxide release. in Free Radical Biology and Medicine. 2005;40(2):226-235.
doi:10.1016/j.freeradbiomed.2005.08.027 .

Harhaji-Trajković, Ljubica, Popadić, Dušan, Miljković, Đorđe, Stojanović, Ivana D., Isaković, Aleksandra, Trajković, Vladimir, "Acidosis affects tumor cell survival through modulation of nitric oxide release" in Free Radical Biology and Medicine, 40, no. 2 (2005):226-235,
https://doi.org/10.1016/j.freeradbiomed.2005.08.027 . .