TY  - JOUR
AU  - Krunić, Matija
AU  - Ristić, Biljana
AU  - Bošnjak, Mihajlo
AU  - Paunović, Verica
AU  - Tovilović-Kovačević, Gordana
AU  - Zogović, Nevena
AU  - Mirčić, Aleksandar
AU  - Marković, Zoran
AU  - Todorović-Marković, Biljana
AU  - Jovanović, Svetlana
AU  - Kleut, Duška
AU  - Mojović, Miloš
AU  - Nakarada, Đura
AU  - Marković, Olivera
AU  - Vuković, Irena
AU  - Harhaji-Trajković, Ljubica
AU  - Trajković, Vladimir
PY  - 2021
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/4812
AB  - We investigated the ability of graphene quantum dot (GQD) nanoparticles to protect SH-SY5Y human neuroblastoma cells from oxidative/nitrosative stress induced by iron-nitrosyl complex sodium nitroprusside (SNP).
GQD reduced SNP cytotoxicity by preventing mitochondrial depolarization, caspase-2 activation, and subsequent apoptotic death. Although GQD diminished the levels of nitric oxide (NO) in SNP-exposed cells, NO scavengers displayed only a slight protective effect, suggesting that NO quenching was not the main protective mechanism of GQD. GQD also reduced SNP-triggered increase in the intracellular levels of hydroxyl radical (•OH), superoxide anion (O2•- ), and lipid peroxidation. Nonselective antioxidants, •OH scavenging, and iron chelators, but not superoxide dismutase, mimicked GQD cytoprotective activity, indicating that GQD protect cells by neutralizing •OH generated in the presence of SNP-released iron. Cellular internalization of GQD was required for optimal protection, since a removal of extracellular GQD by extensive washing only partly diminished their protective effect. Moreover, GQD cooperated with SNP to induce autophagy, as confirmed by the inhibition of autophagylimiting Akt/PRAS40/mTOR signaling and increase in autophagy gene transcription, protein levels of proautophagic beclin-1 and LC3-II, formation of autophagic vesicles, and degradation of autophagic target p62. The antioxidant activity of GQD was not involved in autophagy induction, as antioxidants N-acetylcysteine and dimethyl sulfoxide failed to stimulate autophagy in SNP-exposed cells. Pharmacological inhibitors of early (wortmannin, 3-methyladenine) or late stages of autophagy (NH4Cl) efficiently reduced the protective effect of GQD. Therefore, the ability of GQD to prevent the in vitro neurotoxicity of SNP depends on both •OH/NO scavenging and induction of cytoprotective autophagy.
PB  - Elsevier
T2  - Free Radical Biology and Medicine
T1  - Graphene quantum dot antioxidant and proautophagic actions protect SH-SY5Y neuroblastoma cells from oxidative stress-mediated apoptotic death
VL  - 177
SP  - 167
EP  - 180
DO  - 10.1016/j.freeradbiomed.2021.10.025
ER  - 

@article{
author = "Krunić, Matija and Ristić, Biljana and Bošnjak, Mihajlo and Paunović, Verica and Tovilović-Kovačević, Gordana and Zogović, Nevena and Mirčić, Aleksandar and Marković, Zoran and Todorović-Marković, Biljana and Jovanović, Svetlana and Kleut, Duška and Mojović, Miloš and Nakarada, Đura and Marković, Olivera and Vuković, Irena and Harhaji-Trajković, Ljubica and Trajković, Vladimir",
year = "2021",
abstract = "We investigated the ability of graphene quantum dot (GQD) nanoparticles to protect SH-SY5Y human neuroblastoma cells from oxidative/nitrosative stress induced by iron-nitrosyl complex sodium nitroprusside (SNP).
GQD reduced SNP cytotoxicity by preventing mitochondrial depolarization, caspase-2 activation, and subsequent apoptotic death. Although GQD diminished the levels of nitric oxide (NO) in SNP-exposed cells, NO scavengers displayed only a slight protective effect, suggesting that NO quenching was not the main protective mechanism of GQD. GQD also reduced SNP-triggered increase in the intracellular levels of hydroxyl radical (•OH), superoxide anion (O2•- ), and lipid peroxidation. Nonselective antioxidants, •OH scavenging, and iron chelators, but not superoxide dismutase, mimicked GQD cytoprotective activity, indicating that GQD protect cells by neutralizing •OH generated in the presence of SNP-released iron. Cellular internalization of GQD was required for optimal protection, since a removal of extracellular GQD by extensive washing only partly diminished their protective effect. Moreover, GQD cooperated with SNP to induce autophagy, as confirmed by the inhibition of autophagylimiting Akt/PRAS40/mTOR signaling and increase in autophagy gene transcription, protein levels of proautophagic beclin-1 and LC3-II, formation of autophagic vesicles, and degradation of autophagic target p62. The antioxidant activity of GQD was not involved in autophagy induction, as antioxidants N-acetylcysteine and dimethyl sulfoxide failed to stimulate autophagy in SNP-exposed cells. Pharmacological inhibitors of early (wortmannin, 3-methyladenine) or late stages of autophagy (NH4Cl) efficiently reduced the protective effect of GQD. Therefore, the ability of GQD to prevent the in vitro neurotoxicity of SNP depends on both •OH/NO scavenging and induction of cytoprotective autophagy.",
publisher = "Elsevier",
journal = "Free Radical Biology and Medicine",
title = "Graphene quantum dot antioxidant and proautophagic actions protect SH-SY5Y neuroblastoma cells from oxidative stress-mediated apoptotic death",
volume = "177",
pages = "167-180",
doi = "10.1016/j.freeradbiomed.2021.10.025"
}

Krunić, M., Ristić, B., Bošnjak, M., Paunović, V., Tovilović-Kovačević, G., Zogović, N., Mirčić, A., Marković, Z., Todorović-Marković, B., Jovanović, S., Kleut, D., Mojović, M., Nakarada, Đ., Marković, O., Vuković, I., Harhaji-Trajković, L.,& Trajković, V.. (2021). Graphene quantum dot antioxidant and proautophagic actions protect SH-SY5Y neuroblastoma cells from oxidative stress-mediated apoptotic death. in Free Radical Biology and Medicine
Elsevier., 177, 167-180.
https://doi.org/10.1016/j.freeradbiomed.2021.10.025

Krunić M, Ristić B, Bošnjak M, Paunović V, Tovilović-Kovačević G, Zogović N, Mirčić A, Marković Z, Todorović-Marković B, Jovanović S, Kleut D, Mojović M, Nakarada Đ, Marković O, Vuković I, Harhaji-Trajković L, Trajković V. Graphene quantum dot antioxidant and proautophagic actions protect SH-SY5Y neuroblastoma cells from oxidative stress-mediated apoptotic death. in Free Radical Biology and Medicine. 2021;177:167-180.
doi:10.1016/j.freeradbiomed.2021.10.025 .

Krunić, Matija, Ristić, Biljana, Bošnjak, Mihajlo, Paunović, Verica, Tovilović-Kovačević, Gordana, Zogović, Nevena, Mirčić, Aleksandar, Marković, Zoran, Todorović-Marković, Biljana, Jovanović, Svetlana, Kleut, Duška, Mojović, Miloš, Nakarada, Đura, Marković, Olivera, Vuković, Irena, Harhaji-Trajković, Ljubica, Trajković, Vladimir, "Graphene quantum dot antioxidant and proautophagic actions protect SH-SY5Y neuroblastoma cells from oxidative stress-mediated apoptotic death" in Free Radical Biology and Medicine, 177 (2021):167-180,
https://doi.org/10.1016/j.freeradbiomed.2021.10.025 . .

TY  - JOUR
AU  - Krunić, Matija
AU  - Ristić, Biljana
AU  - Bošnjak, Mihajlo
AU  - Paunović, Verica
AU  - Tovilović-Kovačević, Gordana
AU  - Zogović, Nevena
AU  - Mirčić, Aleksandar
AU  - Marković, Zoran
AU  - Todorović-Marković, Biljana
AU  - Jovanović, Svetlana
AU  - Kleut, Duška
AU  - Mojović, Miloš
AU  - Nakarada, Đura
AU  - Marković, Olivera
AU  - Vuković, Irena
AU  - Harhaji-Trajković, Ljubica
AU  - Trajković, Vladimir
PY  - 2021
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/4818
AB  - We investigated the ability of graphene quantum dot (GQD) nanoparticles to protect SH-SY5Y human neuroblastoma cells from oxidative/nitrosative stress induced by iron-nitrosyl complex sodium nitroprusside (SNP).GQD reduced SNP cytotoxicity by preventing mitochondrial depolarization, caspase-2 activation, and subsequent apoptotic death. Although GQD diminished the levels of nitric oxide (NO) in SNP-exposed cells, NO scavengers displayed only a slight protective effect, suggesting that NO quenching was not the main protective mechanism of GQD. GQD also reduced SNP-triggered increase in the intracellular levels of hydroxyl radical (•OH), superoxide anion (O2•- ), and lipid peroxidation. Nonselective antioxidants, •OH scavenging, and iron chelators, but not superoxide dismutase, mimicked GQD cytoprotective activity, indicating that GQD protect cells by neutralizing •OH generated in the presence of SNP-released iron. Cellular internalization of GQD was required for optimal protection, since a removal of extracellular GQD by extensive washing only partly diminished their protective effect. Moreover, GQD cooperated with SNP to induce autophagy, as confirmed by the inhibition of autophagylimiting Akt/PRAS40/mTOR signaling and increase in autophagy gene transcription, protein levels of proautophagic beclin-1 and LC3-II, formation of autophagic vesicles, and degradation of autophagic target p62. The antioxidant activity of GQD was not involved in autophagy induction, as antioxidants N-acetylcysteine and dimethyl sulfoxide failed to stimulate autophagy in SNP-exposed cells. Pharmacological inhibitors of early (wortmannin, 3-methyladenine) or late stages of autophagy (NH4Cl) efficiently reduced the protective effect of GQD. Therefore, the ability of GQD to prevent the in vitro neurotoxicity of SNP depends on both •OH/NO scavenging and induction of cytoprotective autophagy.
PB  - Elsevier
T2  - Free Radical Biology and Medicine
T1  - Graphene quantum dot antioxidant and proautophagic actions protect SH-SY5Y neuroblastoma cells from oxidative stress-mediated apoptotic death
VL  - 177
SP  - 167
EP  - 180
DO  - 10.1016/j.freeradbiomed.2021.10.025
ER  - 

@article{
author = "Krunić, Matija and Ristić, Biljana and Bošnjak, Mihajlo and Paunović, Verica and Tovilović-Kovačević, Gordana and Zogović, Nevena and Mirčić, Aleksandar and Marković, Zoran and Todorović-Marković, Biljana and Jovanović, Svetlana and Kleut, Duška and Mojović, Miloš and Nakarada, Đura and Marković, Olivera and Vuković, Irena and Harhaji-Trajković, Ljubica and Trajković, Vladimir",
year = "2021",
abstract = "We investigated the ability of graphene quantum dot (GQD) nanoparticles to protect SH-SY5Y human neuroblastoma cells from oxidative/nitrosative stress induced by iron-nitrosyl complex sodium nitroprusside (SNP).GQD reduced SNP cytotoxicity by preventing mitochondrial depolarization, caspase-2 activation, and subsequent apoptotic death. Although GQD diminished the levels of nitric oxide (NO) in SNP-exposed cells, NO scavengers displayed only a slight protective effect, suggesting that NO quenching was not the main protective mechanism of GQD. GQD also reduced SNP-triggered increase in the intracellular levels of hydroxyl radical (•OH), superoxide anion (O2•- ), and lipid peroxidation. Nonselective antioxidants, •OH scavenging, and iron chelators, but not superoxide dismutase, mimicked GQD cytoprotective activity, indicating that GQD protect cells by neutralizing •OH generated in the presence of SNP-released iron. Cellular internalization of GQD was required for optimal protection, since a removal of extracellular GQD by extensive washing only partly diminished their protective effect. Moreover, GQD cooperated with SNP to induce autophagy, as confirmed by the inhibition of autophagylimiting Akt/PRAS40/mTOR signaling and increase in autophagy gene transcription, protein levels of proautophagic beclin-1 and LC3-II, formation of autophagic vesicles, and degradation of autophagic target p62. The antioxidant activity of GQD was not involved in autophagy induction, as antioxidants N-acetylcysteine and dimethyl sulfoxide failed to stimulate autophagy in SNP-exposed cells. Pharmacological inhibitors of early (wortmannin, 3-methyladenine) or late stages of autophagy (NH4Cl) efficiently reduced the protective effect of GQD. Therefore, the ability of GQD to prevent the in vitro neurotoxicity of SNP depends on both •OH/NO scavenging and induction of cytoprotective autophagy.",
publisher = "Elsevier",
journal = "Free Radical Biology and Medicine",
title = "Graphene quantum dot antioxidant and proautophagic actions protect SH-SY5Y neuroblastoma cells from oxidative stress-mediated apoptotic death",
volume = "177",
pages = "167-180",
doi = "10.1016/j.freeradbiomed.2021.10.025"
}

Krunić, M., Ristić, B., Bošnjak, M., Paunović, V., Tovilović-Kovačević, G., Zogović, N., Mirčić, A., Marković, Z., Todorović-Marković, B., Jovanović, S., Kleut, D., Mojović, M., Nakarada, Đ., Marković, O., Vuković, I., Harhaji-Trajković, L.,& Trajković, V.. (2021). Graphene quantum dot antioxidant and proautophagic actions protect SH-SY5Y neuroblastoma cells from oxidative stress-mediated apoptotic death. in Free Radical Biology and Medicine
Elsevier., 177, 167-180.
https://doi.org/10.1016/j.freeradbiomed.2021.10.025

Krunić M, Ristić B, Bošnjak M, Paunović V, Tovilović-Kovačević G, Zogović N, Mirčić A, Marković Z, Todorović-Marković B, Jovanović S, Kleut D, Mojović M, Nakarada Đ, Marković O, Vuković I, Harhaji-Trajković L, Trajković V. Graphene quantum dot antioxidant and proautophagic actions protect SH-SY5Y neuroblastoma cells from oxidative stress-mediated apoptotic death. in Free Radical Biology and Medicine. 2021;177:167-180.
doi:10.1016/j.freeradbiomed.2021.10.025 .

Krunić, Matija, Ristić, Biljana, Bošnjak, Mihajlo, Paunović, Verica, Tovilović-Kovačević, Gordana, Zogović, Nevena, Mirčić, Aleksandar, Marković, Zoran, Todorović-Marković, Biljana, Jovanović, Svetlana, Kleut, Duška, Mojović, Miloš, Nakarada, Đura, Marković, Olivera, Vuković, Irena, Harhaji-Trajković, Ljubica, Trajković, Vladimir, "Graphene quantum dot antioxidant and proautophagic actions protect SH-SY5Y neuroblastoma cells from oxidative stress-mediated apoptotic death" in Free Radical Biology and Medicine, 177 (2021):167-180,
https://doi.org/10.1016/j.freeradbiomed.2021.10.025 . .

TY  - JOUR
AU  - Tovilović, Gordana
AU  - Zogovic, Nevena
AU  - Šoškić, Vukić
AU  - Schrattenholz, Andre
AU  - Kostić Rajačić, Slađana
AU  - Misirkić-Marjanović, Maja
AU  - Janjetovic, Kristina
AU  - Vucicevic, Ljubica
AU  - Arsikin, Katarina
AU  - Harhaji-Trajković, Ljubica
AU  - Trajković, Vladimir
PY  - 2013
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/1201
AB  - We investigated the ability of 19 recently synthesized arylpiperazine compounds to protect human SH-SY5Y 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-associAed LC3-II, as well as intracytoplasmic acidification induced by 6-OHDA. The inhibition of autophagy using LC3 beta 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 ERR 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 6-0HDA-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  - Oxford : Pergamon-Elsevier Science Ltd
T2  - Neuropharmacology
T1  - Arylpiperazine-mediated activation of Akt protects SH-SY5Y neuroblastoma cells from 6-hydroxydopamine-induced apoptotic and autophagic death
VL  - 72
SP  - 224
EP  - 235
DO  - 10.1016/j.neuropharm.2013.04.037
ER  - 

@article{
author = "Tovilović, Gordana and Zogovic, Nevena and Šoškić, Vukić and Schrattenholz, Andre and Kostić Rajačić, Slađana and Misirkić-Marjanović, Maja and Janjetovic, Kristina and Vucicevic, 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 SH-SY5Y 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-associAed LC3-II, as well as intracytoplasmic acidification induced by 6-OHDA. The inhibition of autophagy using LC3 beta 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 ERR 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 6-0HDA-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 = "Oxford : Pergamon-Elsevier Science Ltd",
journal = "Neuropharmacology",
title = "Arylpiperazine-mediated activation of Akt protects SH-SY5Y neuroblastoma cells from 6-hydroxydopamine-induced apoptotic and autophagic death",
volume = "72",
pages = "224-235",
doi = "10.1016/j.neuropharm.2013.04.037"
}

Tovilović, G., Zogovic, N., Šoškić, V., Schrattenholz, A., Kostić Rajačić, S., Misirkić-Marjanović, M., Janjetovic, K., Vucicevic, 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
Oxford : Pergamon-Elsevier Science Ltd., 72, 224-235.
https://doi.org/10.1016/j.neuropharm.2013.04.037

Tovilović G, Zogovic N, Šoškić V, Schrattenholz A, Kostić Rajačić S, Misirkić-Marjanović M, Janjetovic K, Vucicevic 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, Gordana, Zogovic, Nevena, Šoškić, Vukić, Schrattenholz, Andre, Kostić Rajačić, Slađana, Misirkić-Marjanović, Maja, Janjetovic, Kristina, Vucicevic, 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  - JOUR
AU  - Tovilović, Gordana
AU  - Zogovic, Nevena
AU  - Harhaji-Trajković, Ljubica
AU  - Misirkić-Marjanović, Maja
AU  - Janjetovic, Kristina
AU  - Vucicevic, Ljubica
AU  - Kostić Rajačić, Slađana
AU  - Schrattenholz, Andre
AU  - Isaković, Aleksandra
AU  - Šoškić, Vukić
AU  - Trajković, Vladimir
PY  - 2012
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/1037
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  - Wiley-V C H Verlag Gmbh, Weinheim
T2  - Chemmedchem
T1  - Arylpiperazine Dopamineric Ligands Protect Neuroblastoma Cells from Nitric Oxide (NO)-Induced Mitochondrial Damage and Apoptosis
VL  - 7
IS  - 3
SP  - 495
EP  - 508
DO  - 10.1002/cmdc.201100537
ER  - 

@article{
author = "Tovilović, Gordana and Zogovic, Nevena and Harhaji-Trajković, Ljubica and Misirkić-Marjanović, Maja and Janjetovic, Kristina and Vucicevic, 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 = "Wiley-V C H Verlag Gmbh, Weinheim",
journal = "Chemmedchem",
title = "Arylpiperazine Dopamineric Ligands Protect Neuroblastoma Cells from Nitric Oxide (NO)-Induced Mitochondrial Damage and Apoptosis",
volume = "7",
number = "3",
pages = "495-508",
doi = "10.1002/cmdc.201100537"
}

Tovilović, G., Zogovic, N., Harhaji-Trajković, L., Misirkić-Marjanović, M., Janjetovic, K., Vucicevic, 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
Wiley-V C H Verlag Gmbh, Weinheim., 7(3), 495-508.
https://doi.org/10.1002/cmdc.201100537

Tovilović G, Zogovic N, Harhaji-Trajković L, Misirkić-Marjanović M, Janjetovic K, Vucicevic 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, Gordana, Zogovic, Nevena, Harhaji-Trajković, Ljubica, Misirkić-Marjanović, Maja, Janjetovic, Kristina, Vucicevic, 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  - Harhaji-Trajković, Ljubica
AU  - Mijatović, Sanja
AU  - Maksimović-Ivanić, Danijela D.
AU  - Stojanovic, I.D.
AU  - Momcilovic, M.B.
AU  - Tufegdžić, Srđan
AU  - Maksimović, Vesna M.
AU  - Marjanovi, Z.S.
AU  - Stosic-Grujicic, S.D.
PY  - 2009
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/616
AB  - Anticancer activities of various extracts of the medicinal mushroom, Ganoderma lucidum, have been widely demonstrated and are mainly associated with the presence of different bioactive polysaccharides and triterpenoids. We have evaluated and compared in vitro and in vivo the antitumor effects of two preparations from Ganoderma lucidum: a methanol extract containing total terpenoids (GLme) and a purified methanol extract containing mainly acidic terpenoids (GLpme). Both extracts inhibited tumor growth of B16 mouse melanoma cells inoculated subcutaneously into syngeneic C57BL/6 mice and reduced viability of B16 cells in vitro, whereby GLme exhibited stronger effect. Furthermore, anticancer activity of GLme was demonstrated for the first time against two other rodent tumor cell lines, L929-mouse fibrosarcoma and C6-rat astrocytoma. The mechanism of antitumor activity of GLme comprised inhibition of cell proliferation and induction of caspase-dependent apoptotic cell death mediated by upregulated p53 and inhibited Bcl-2 expression. Moreover, the antitumor effect of the GLme was associated with intensified production of reactive oxygen species, whereas their neutralization by the antioxidant, N-acetyl cysteine, resulted in partial recovery of cell viability. Thus, our results suggest that GLme might be a good candidate for treatment of diverse forms of cancers.
T2  - Nutrition and Cancer
T1  - Anticancer properties of ganoderma lucidum methanol extracts in vitro and in vivo
VL  - 61
IS  - 5
SP  - 696
EP  - 707
DO  - 10.1080/01635580902898743
ER  - 

@article{
author = "Harhaji-Trajković, Ljubica and Mijatović, Sanja and Maksimović-Ivanić, Danijela D. and Stojanovic, I.D. and Momcilovic, M.B. and Tufegdžić, Srđan and Maksimović, Vesna M. and Marjanovi, Z.S. and Stosic-Grujicic, S.D.",
year = "2009",
abstract = "Anticancer activities of various extracts of the medicinal mushroom, Ganoderma lucidum, have been widely demonstrated and are mainly associated with the presence of different bioactive polysaccharides and triterpenoids. We have evaluated and compared in vitro and in vivo the antitumor effects of two preparations from Ganoderma lucidum: a methanol extract containing total terpenoids (GLme) and a purified methanol extract containing mainly acidic terpenoids (GLpme). Both extracts inhibited tumor growth of B16 mouse melanoma cells inoculated subcutaneously into syngeneic C57BL/6 mice and reduced viability of B16 cells in vitro, whereby GLme exhibited stronger effect. Furthermore, anticancer activity of GLme was demonstrated for the first time against two other rodent tumor cell lines, L929-mouse fibrosarcoma and C6-rat astrocytoma. The mechanism of antitumor activity of GLme comprised inhibition of cell proliferation and induction of caspase-dependent apoptotic cell death mediated by upregulated p53 and inhibited Bcl-2 expression. Moreover, the antitumor effect of the GLme was associated with intensified production of reactive oxygen species, whereas their neutralization by the antioxidant, N-acetyl cysteine, resulted in partial recovery of cell viability. Thus, our results suggest that GLme might be a good candidate for treatment of diverse forms of cancers.",
journal = "Nutrition and Cancer",
title = "Anticancer properties of ganoderma lucidum methanol extracts in vitro and in vivo",
volume = "61",
number = "5",
pages = "696-707",
doi = "10.1080/01635580902898743"
}

Harhaji-Trajković, L., Mijatović, S., Maksimović-Ivanić, D. D., Stojanovic, I.D., Momcilovic, M.B., Tufegdžić, S., Maksimović, V. M., Marjanovi, Z.S.,& Stosic-Grujicic, S.D.. (2009). Anticancer properties of ganoderma lucidum methanol extracts in vitro and in vivo. in Nutrition and Cancer, 61(5), 696-707.
https://doi.org/10.1080/01635580902898743

Harhaji-Trajković L, Mijatović S, Maksimović-Ivanić DD, Stojanovic I, Momcilovic M, Tufegdžić S, Maksimović VM, Marjanovi Z, Stosic-Grujicic S. Anticancer properties of ganoderma lucidum methanol extracts in vitro and in vivo. in Nutrition and Cancer. 2009;61(5):696-707.
doi:10.1080/01635580902898743 .

Harhaji-Trajković, Ljubica, Mijatović, Sanja, Maksimović-Ivanić, Danijela D., Stojanovic, I.D., Momcilovic, M.B., Tufegdžić, Srđan, Maksimović, Vesna M., Marjanovi, Z.S., Stosic-Grujicic, S.D., "Anticancer properties of ganoderma lucidum methanol extracts in vitro and in vivo" in Nutrition and Cancer, 61, no. 5 (2009):696-707,
https://doi.org/10.1080/01635580902898743 . .

TY  - JOUR
AU  - Isaković, Aleksandra
AU  - Janković, Teodora
AU  - Harhaji, Ljubica
AU  - Kostić Rajačić, Slađana
AU  - Nikolić, Zoran
AU  - Vajs, Vlatka
AU  - Trajković, Vladimir
PY  - 2008
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/478
AB  - The present study identifies xanthones gentiakochianin and gentiacaulein as the active principles responsible for the in vitro antiglioma action of ether and methanolic extracts of the plant Gentiana kochiana. Gentiakochianin and gentiacaulein induced cell cycle arrest in G2/M and G0/G1 phases, respectively, in both C6 rat glioma and U251 human glioma cell lines. The more efficient antiproliferative action of gentiakochianin was associated with its ability to induce microtubule stabilization in a cell-free assay. Both the xanthones reduced mitochondrial membrane potential and increased the production of reactive oxygen species in glioma cells, but only the effects of gentiakochianin were pronounced enough to cause caspase activation and subsequent apoptotic cell death. The assessment of structure-activity relationship in a series of structurally related xanthones from G. kochiana and Gentianella austriaca revealed dihydroxylation at positions 7, 8 of the xanthonic nucleus as the key structural feature responsible for the ability of gentiakochianin to induce microtubule-associated G2/M cell block and apoptotic cell death in glioma cells.
PB  - Oxford : Pergamon-Elsevier Science Ltd
T2  - Bioorganic and Medicinal Chemistry
T1  - Antiglioma action of xanthones from Gentiana kochiana: Mechanistic and structure-activity requirements
VL  - 16
IS  - 10
SP  - 5683
EP  - 5694
DO  - 10.1016/j.bmc.2008.03.069
ER  - 

@article{
author = "Isaković, Aleksandra and Janković, Teodora and Harhaji, Ljubica and Kostić Rajačić, Slađana and Nikolić, Zoran and Vajs, Vlatka and Trajković, Vladimir",
year = "2008",
abstract = "The present study identifies xanthones gentiakochianin and gentiacaulein as the active principles responsible for the in vitro antiglioma action of ether and methanolic extracts of the plant Gentiana kochiana. Gentiakochianin and gentiacaulein induced cell cycle arrest in G2/M and G0/G1 phases, respectively, in both C6 rat glioma and U251 human glioma cell lines. The more efficient antiproliferative action of gentiakochianin was associated with its ability to induce microtubule stabilization in a cell-free assay. Both the xanthones reduced mitochondrial membrane potential and increased the production of reactive oxygen species in glioma cells, but only the effects of gentiakochianin were pronounced enough to cause caspase activation and subsequent apoptotic cell death. The assessment of structure-activity relationship in a series of structurally related xanthones from G. kochiana and Gentianella austriaca revealed dihydroxylation at positions 7, 8 of the xanthonic nucleus as the key structural feature responsible for the ability of gentiakochianin to induce microtubule-associated G2/M cell block and apoptotic cell death in glioma cells.",
publisher = "Oxford : Pergamon-Elsevier Science Ltd",
journal = "Bioorganic and Medicinal Chemistry",
title = "Antiglioma action of xanthones from Gentiana kochiana: Mechanistic and structure-activity requirements",
volume = "16",
number = "10",
pages = "5683-5694",
doi = "10.1016/j.bmc.2008.03.069"
}

Isaković, A., Janković, T., Harhaji, L., Kostić Rajačić, S., Nikolić, Z., Vajs, V.,& Trajković, V.. (2008). Antiglioma action of xanthones from Gentiana kochiana: Mechanistic and structure-activity requirements. in Bioorganic and Medicinal Chemistry
Oxford : Pergamon-Elsevier Science Ltd., 16(10), 5683-5694.
https://doi.org/10.1016/j.bmc.2008.03.069

Isaković A, Janković T, Harhaji L, Kostić Rajačić S, Nikolić Z, Vajs V, Trajković V. Antiglioma action of xanthones from Gentiana kochiana: Mechanistic and structure-activity requirements. in Bioorganic and Medicinal Chemistry. 2008;16(10):5683-5694.
doi:10.1016/j.bmc.2008.03.069 .

Isaković, Aleksandra, Janković, Teodora, Harhaji, Ljubica, Kostić Rajačić, Slađana, Nikolić, Zoran, Vajs, Vlatka, Trajković, Vladimir, "Antiglioma action of xanthones from Gentiana kochiana: Mechanistic and structure-activity requirements" in Bioorganic and Medicinal Chemistry, 16, no. 10 (2008):5683-5694,
https://doi.org/10.1016/j.bmc.2008.03.069 . .

TY  - JOUR
AU  - Isaković, Aleksandra
AU  - Marković, Zoran M.
AU  - Nikolić, Nadežda
AU  - Todorović-Marković, Biljana
AU  - Vranješ-Đurić, Sanja
AU  - Harhaji, Ljubica
AU  - Raičević, Nevena
AU  - Romčević, Nebojša
AU  - Vasiljević-Radović, Dana
AU  - Dramićanin, Miroslav
AU  - Trajković, Vladimir
PY  - 2006
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/4120
AB  - We investigated the effect of γ-irradiation on the cytotoxicity of pure C 60 solubilized in water by using tetrahydrofuran (THF/n-C 60 or THF/n-C 60 ). In contrast to THF/n-C 60 , its γ-irradiated counterpart failed to generate oxygen radicals and cause extracellular signal-regulated kinase (ERK)-dependent necrotic cell death in various types of mammalian cells. Moreover, γ-irradiated THF/n-C 60 protected cells from the oxidative stress induced by native THF/n-C 60 or hydrogen peroxide. The observed biological effects were associated with γ-irradiation-mediated decomposition of THF and subsequent derivatization of the n-C 60 surface. These results for the first time demonstrate γ-irradiation-mediated changes in the physico-chemical properties of THF-prepared nanocrystalline C 60 , resulting in a complete loss of its cytotoxic effect and its conversion to a cytoprotective agent.
PB  - Elsevier
T2  - Biomaterials
T1  - Inactivation of nanocrystalline C60 cytotoxicity by γ-irradiation
VL  - 27
IS  - 29
SP  - 5049
EP  - 5058
DO  - 10.1016/j.biomaterials.2006.05.047
ER  - 

@article{
author = "Isaković, Aleksandra and Marković, Zoran M. and Nikolić, Nadežda and Todorović-Marković, Biljana and Vranješ-Đurić, Sanja and Harhaji, Ljubica and Raičević, Nevena and Romčević, Nebojša and Vasiljević-Radović, Dana and Dramićanin, Miroslav and Trajković, Vladimir",
year = "2006",
abstract = "We investigated the effect of γ-irradiation on the cytotoxicity of pure C 60 solubilized in water by using tetrahydrofuran (THF/n-C 60 or THF/n-C 60 ). In contrast to THF/n-C 60 , its γ-irradiated counterpart failed to generate oxygen radicals and cause extracellular signal-regulated kinase (ERK)-dependent necrotic cell death in various types of mammalian cells. Moreover, γ-irradiated THF/n-C 60 protected cells from the oxidative stress induced by native THF/n-C 60 or hydrogen peroxide. The observed biological effects were associated with γ-irradiation-mediated decomposition of THF and subsequent derivatization of the n-C 60 surface. These results for the first time demonstrate γ-irradiation-mediated changes in the physico-chemical properties of THF-prepared nanocrystalline C 60 , resulting in a complete loss of its cytotoxic effect and its conversion to a cytoprotective agent.",
publisher = "Elsevier",
journal = "Biomaterials",
title = "Inactivation of nanocrystalline C60 cytotoxicity by γ-irradiation",
volume = "27",
number = "29",
pages = "5049-5058",
doi = "10.1016/j.biomaterials.2006.05.047"
}

Isaković, A., Marković, Z. M., Nikolić, N., Todorović-Marković, B., Vranješ-Đurić, S., Harhaji, L., Raičević, N., Romčević, N., Vasiljević-Radović, D., Dramićanin, M.,& Trajković, V.. (2006). Inactivation of nanocrystalline C60 cytotoxicity by γ-irradiation. in Biomaterials
Elsevier., 27(29), 5049-5058.
https://doi.org/10.1016/j.biomaterials.2006.05.047

Isaković A, Marković ZM, Nikolić N, Todorović-Marković B, Vranješ-Đurić S, Harhaji L, Raičević N, Romčević N, Vasiljević-Radović D, Dramićanin M, Trajković V. Inactivation of nanocrystalline C60 cytotoxicity by γ-irradiation. in Biomaterials. 2006;27(29):5049-5058.
doi:10.1016/j.biomaterials.2006.05.047 .

Isaković, Aleksandra, Marković, Zoran M., Nikolić, Nadežda, Todorović-Marković, Biljana, Vranješ-Đurić, Sanja, Harhaji, Ljubica, Raičević, Nevena, Romčević, Nebojša, Vasiljević-Radović, Dana, Dramićanin, Miroslav, Trajković, Vladimir, "Inactivation of nanocrystalline C60 cytotoxicity by γ-irradiation" in Biomaterials, 27, no. 29 (2006):5049-5058,
https://doi.org/10.1016/j.biomaterials.2006.05.047 . .