TY  - CONF
AU  - Ristić, Biljana
AU  - Krunić, Matija
AU  - Bošnjak, Mihajlo
AU  - Mirčić, Aleksandar
AU  - Tovilović-Kovačević, Gordana
AU  - Zogović, Nevena
AU  - Paunović, Verica
AU  - Trajković, Vladimir
AU  - Harhaji-Trajković, Ljubica
PY  - 2019
UR  - https://nordicautophagy.org/
UR  - https://nordicautophagy.org/report-3rd-nordic-autophagy-society-conference-in-utrecht/
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6718
AB  - We investigated the ability of nano-sized graphen layers graphen quantum dots (GQD) to protect human neuroblastoma SH-SY5Y cells from toxicity of NO donor sodium nitroprusside (SNP). GQD prevented SNP induced mitochondrial depolarization and caspase dependent apoptosis. GQD partly suppressed neurotoxicity of NO donor DEA-NONOate and reduced SNP induced NO release in cells and cell-free system, suggesting that neuroprotective effects of GQD were partly mediated by their NO-scavanging capacity. However, GQD significantly preserved SH-SY5Y cells from light exhausted SNP, which was unable to produce NO, implying the existence of protective mechanism independent of NO-scavenging. Unspecific antioxidant, as well as hydroxyl radical (.OH) scavengers DMSO, vitamin E and gluthatione mimicked neuroprotective activity of GQD, while GQD diminished concentration of reactive oxygen species (ROS), especially .OH, in cells and cell culture medium, suggesting important role of .OH scavenging in neuroprotective activity of GQD. However ability of GQD to protect SH-SY5Y cells from SNP was not exclusively mediated by their ability to scavenge NO and ROS from medium, since it persisted after washing of GQD preincubated cells. Interestingly, GQD were found to be present in autophagosome-like vacuoles. Both SNP and GQD, and especially their combination, increased intracellular acidity characteristic for presence of autophagosomes, concentration of proautophagic protein beclin-1, while deacreased level of specific substrate of autophagic proteolysis p62. Moreover, SNP and GQD, and above all their combination, increased concentration of autophagosome-associated protein LC3 II in the presence of inhibitor of autophagic proteolysis bafilomycin A1. Finally, autophagy inhibitors 3-methzladenine, wortmannin and NH4Cl prevented neuroprotective ability of GQD, implying that GQD stimulated prosurvival autophagy in SNP treated neurons. Therefore, by demonstrating ability of GQD to protect SH-SY5Y neurons from SNP induced apoptosis by scavenging NO/ROS and stimulation of cytoprotective autophagy, our results suggest that GQD could be valuable candidate for treatment of neurodegenerative disorders.
PB  - Nordic Autophagy Society
C3  - 3rd Nordic Autophagy Society (NAS) Conference; 2019 May 22-24; Utrecht, Netherlands
T1  - Neuroprotective activity of GQD against SNP-induced toxicity are mediated by ROS/RNS scavenging and protective autophagy induction
SP  - 40
EP  - 40
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_6718
ER  - 

@conference{
author = "Ristić, Biljana and Krunić, Matija and Bošnjak, Mihajlo and Mirčić, Aleksandar and Tovilović-Kovačević, Gordana and Zogović, Nevena and Paunović, Verica and Trajković, Vladimir and Harhaji-Trajković, Ljubica",
year = "2019",
abstract = "We investigated the ability of nano-sized graphen layers graphen quantum dots (GQD) to protect human neuroblastoma SH-SY5Y cells from toxicity of NO donor sodium nitroprusside (SNP). GQD prevented SNP induced mitochondrial depolarization and caspase dependent apoptosis. GQD partly suppressed neurotoxicity of NO donor DEA-NONOate and reduced SNP induced NO release in cells and cell-free system, suggesting that neuroprotective effects of GQD were partly mediated by their NO-scavanging capacity. However, GQD significantly preserved SH-SY5Y cells from light exhausted SNP, which was unable to produce NO, implying the existence of protective mechanism independent of NO-scavenging. Unspecific antioxidant, as well as hydroxyl radical (.OH) scavengers DMSO, vitamin E and gluthatione mimicked neuroprotective activity of GQD, while GQD diminished concentration of reactive oxygen species (ROS), especially .OH, in cells and cell culture medium, suggesting important role of .OH scavenging in neuroprotective activity of GQD. However ability of GQD to protect SH-SY5Y cells from SNP was not exclusively mediated by their ability to scavenge NO and ROS from medium, since it persisted after washing of GQD preincubated cells. Interestingly, GQD were found to be present in autophagosome-like vacuoles. Both SNP and GQD, and especially their combination, increased intracellular acidity characteristic for presence of autophagosomes, concentration of proautophagic protein beclin-1, while deacreased level of specific substrate of autophagic proteolysis p62. Moreover, SNP and GQD, and above all their combination, increased concentration of autophagosome-associated protein LC3 II in the presence of inhibitor of autophagic proteolysis bafilomycin A1. Finally, autophagy inhibitors 3-methzladenine, wortmannin and NH4Cl prevented neuroprotective ability of GQD, implying that GQD stimulated prosurvival autophagy in SNP treated neurons. Therefore, by demonstrating ability of GQD to protect SH-SY5Y neurons from SNP induced apoptosis by scavenging NO/ROS and stimulation of cytoprotective autophagy, our results suggest that GQD could be valuable candidate for treatment of neurodegenerative disorders.",
publisher = "Nordic Autophagy Society",
journal = "3rd Nordic Autophagy Society (NAS) Conference; 2019 May 22-24; Utrecht, Netherlands",
title = "Neuroprotective activity of GQD against SNP-induced toxicity are mediated by ROS/RNS scavenging and protective autophagy induction",
pages = "40-40",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_6718"
}

Ristić, B., Krunić, M., Bošnjak, M., Mirčić, A., Tovilović-Kovačević, G., Zogović, N., Paunović, V., Trajković, V.,& Harhaji-Trajković, L.. (2019). Neuroprotective activity of GQD against SNP-induced toxicity are mediated by ROS/RNS scavenging and protective autophagy induction. in 3rd Nordic Autophagy Society (NAS) Conference; 2019 May 22-24; Utrecht, Netherlands
Nordic Autophagy Society., 40-40.
https://hdl.handle.net/21.15107/rcub_ibiss_6718

Ristić B, Krunić M, Bošnjak M, Mirčić A, Tovilović-Kovačević G, Zogović N, Paunović V, Trajković V, Harhaji-Trajković L. Neuroprotective activity of GQD against SNP-induced toxicity are mediated by ROS/RNS scavenging and protective autophagy induction. in 3rd Nordic Autophagy Society (NAS) Conference; 2019 May 22-24; Utrecht, Netherlands. 2019;:40-40.
https://hdl.handle.net/21.15107/rcub_ibiss_6718 .

Ristić, Biljana, Krunić, Matija, Bošnjak, Mihajlo, Mirčić, Aleksandar, Tovilović-Kovačević, Gordana, Zogović, Nevena, Paunović, Verica, Trajković, Vladimir, Harhaji-Trajković, Ljubica, "Neuroprotective activity of GQD against SNP-induced toxicity are mediated by ROS/RNS scavenging and protective autophagy induction" in 3rd Nordic Autophagy Society (NAS) Conference; 2019 May 22-24; Utrecht, Netherlands (2019):40-40,
https://hdl.handle.net/21.15107/rcub_ibiss_6718 .

TY  - CONF
AU  - Bošnjak, Mihajlo
AU  - Ristić, Biljana
AU  - Krunić, Matija
AU  - Mirčić, Aleksandar
AU  - Zogović, Nevena
AU  - Tovilović-Kovačević, Gordana
AU  - Paunović, Verica
AU  - Trajković, Vladimir
AU  - Harhaji-Trajković, Ljubica
PY  - 2019
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6341
AB  - We here investigated protective potential of nanoparticles graphene quantum dots
(GQD) against neurotoxicity of sodium nitroprusside (SNP), NO-donor and
antihypertensive drug widely used in studies of nitrosative stress-induced
neurotoxicity. GQD prevented SNP-induced apoptosis, caspase activation and
mitochondrial depolarization in SH-SY5Y neuroblastoma cells. GQD decreased SNP
generated nitrite accumulation in supernatants, as well as NO/ONOO- concentrations
in cells and cell-free medium. However, ONOO- and NO scavengers only slightly
suppressed SNP neurotoxicity. Moreover, light exhausted SNP, incapable of producing
NO, was toxic to SH-SY5Y cells, while GQD strongly reduced its neurotoxicity,
suggesting that defensive effect of GQD far exceeded their NO scavenging activity.
FeSO4 increased death of SH-SY5Y cells, while iron chelators decreased toxicity of
iron-containing SNP. GQD neutralized SNP generated reactive oxygen species (ROS)
production, particularly O2•− and •OH in both cells and cell-free condition.
Neurotoxicity of SNP was suppressed in the presence of unspecific antioxidants,
scavengers of •OH and lipid hydroperoxyl radicals, while it was increased with •OH
generating superoxide dismutase (SOD). Intracellular localization of GQD was
confirmed by transmission electron microscopy (TEM), while extensive washing of
cells preincubated with GQD, only partly reduced their protective activity, suggesting
that GQD exerted neuroprotective effect both intra- and extracellularly. Taken together,
these results suggested that GQD protected neuroblastoma cells by neutralizing reactive
nitrogen species (RNS) and ROS, predominantly •OH formed in Fenton reaction
catalyzed by iron derived from SNP. Therefore, GQD might be promising choice for
treatment of ROS/RNS-mediated neurodegenerative diseases.
PB  - Belgrade: Institute for Biological Research "Siniša Stanković"– National Institute of Republic of Serbia, University of Belgrade
C3  - Immunology at the Confluence of Multidisciplinary Approaches: abstract book: 2019 Dec 6-8; Belgrade, Serbia
T1  - Graphene quantum dots protect SH-SY5Y cells from SNP induced apoptosis by scavenging reactive oxygen and nitrogen species
SP  - 37
EP  - 37
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_6341
ER  - 

@conference{
author = "Bošnjak, Mihajlo and Ristić, Biljana and Krunić, Matija and Mirčić, Aleksandar and Zogović, Nevena and Tovilović-Kovačević, Gordana and Paunović, Verica and Trajković, Vladimir and Harhaji-Trajković, Ljubica",
year = "2019",
abstract = "We here investigated protective potential of nanoparticles graphene quantum dots
(GQD) against neurotoxicity of sodium nitroprusside (SNP), NO-donor and
antihypertensive drug widely used in studies of nitrosative stress-induced
neurotoxicity. GQD prevented SNP-induced apoptosis, caspase activation and
mitochondrial depolarization in SH-SY5Y neuroblastoma cells. GQD decreased SNP
generated nitrite accumulation in supernatants, as well as NO/ONOO- concentrations
in cells and cell-free medium. However, ONOO- and NO scavengers only slightly
suppressed SNP neurotoxicity. Moreover, light exhausted SNP, incapable of producing
NO, was toxic to SH-SY5Y cells, while GQD strongly reduced its neurotoxicity,
suggesting that defensive effect of GQD far exceeded their NO scavenging activity.
FeSO4 increased death of SH-SY5Y cells, while iron chelators decreased toxicity of
iron-containing SNP. GQD neutralized SNP generated reactive oxygen species (ROS)
production, particularly O2•− and •OH in both cells and cell-free condition.
Neurotoxicity of SNP was suppressed in the presence of unspecific antioxidants,
scavengers of •OH and lipid hydroperoxyl radicals, while it was increased with •OH
generating superoxide dismutase (SOD). Intracellular localization of GQD was
confirmed by transmission electron microscopy (TEM), while extensive washing of
cells preincubated with GQD, only partly reduced their protective activity, suggesting
that GQD exerted neuroprotective effect both intra- and extracellularly. Taken together,
these results suggested that GQD protected neuroblastoma cells by neutralizing reactive
nitrogen species (RNS) and ROS, predominantly •OH formed in Fenton reaction
catalyzed by iron derived from SNP. Therefore, GQD might be promising choice for
treatment of ROS/RNS-mediated neurodegenerative diseases.",
publisher = "Belgrade: Institute for Biological Research "Siniša Stanković"– National Institute of Republic of Serbia, University of Belgrade",
journal = "Immunology at the Confluence of Multidisciplinary Approaches: abstract book: 2019 Dec 6-8; Belgrade, Serbia",
title = "Graphene quantum dots protect SH-SY5Y cells from SNP induced apoptosis by scavenging reactive oxygen and nitrogen species",
pages = "37-37",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_6341"
}

Bošnjak, M., Ristić, B., Krunić, M., Mirčić, A., Zogović, N., Tovilović-Kovačević, G., Paunović, V., Trajković, V.,& Harhaji-Trajković, L.. (2019). Graphene quantum dots protect SH-SY5Y cells from SNP induced apoptosis by scavenging reactive oxygen and nitrogen species. in Immunology at the Confluence of Multidisciplinary Approaches: abstract book: 2019 Dec 6-8; Belgrade, Serbia
Belgrade: Institute for Biological Research "Siniša Stanković"– National Institute of Republic of Serbia, University of Belgrade., 37-37.
https://hdl.handle.net/21.15107/rcub_ibiss_6341

Bošnjak M, Ristić B, Krunić M, Mirčić A, Zogović N, Tovilović-Kovačević G, Paunović V, Trajković V, Harhaji-Trajković L. Graphene quantum dots protect SH-SY5Y cells from SNP induced apoptosis by scavenging reactive oxygen and nitrogen species. in Immunology at the Confluence of Multidisciplinary Approaches: abstract book: 2019 Dec 6-8; Belgrade, Serbia. 2019;:37-37.
https://hdl.handle.net/21.15107/rcub_ibiss_6341 .

Bošnjak, Mihajlo, Ristić, Biljana, Krunić, Matija, Mirčić, Aleksandar, Zogović, Nevena, Tovilović-Kovačević, Gordana, Paunović, Verica, Trajković, Vladimir, Harhaji-Trajković, Ljubica, "Graphene quantum dots protect SH-SY5Y cells from SNP induced apoptosis by scavenging reactive oxygen and nitrogen species" in Immunology at the Confluence of Multidisciplinary Approaches: abstract book: 2019 Dec 6-8; Belgrade, Serbia (2019):37-37,
https://hdl.handle.net/21.15107/rcub_ibiss_6341 .

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

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

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

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

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

TY  - JOUR
AU  - Stojković Burić, Sonja
AU  - Podolski-Renić, Ana
AU  - Dinić, Jelena
AU  - Stanković, Tijana
AU  - Banković, Jasna Z.
AU  - Hadzic, Stefan
AU  - Paunovic, Verica
AU  - Isakovic, Aleksandra
AU  - Tanić, Nikola
AU  - Pešić, Milica
PY  - 2015
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/4046
AB  - Chemoresistance is a severe limitation to glioblastoma (GBM) therapy and there is a strong need to understand the underlying mechanisms that determine its response to different chemotherapeutics. Therefore, we induced resistance in C6 rat glioma cell line, which considerably resembles the characteristics of human GBM. The resistant phenotype was developed by 3-bis (2-chloroethyl)-1-nitrosourea (BCNU), one of the most commonly used therapeutic drug in the course of GBM treatment. After confirmation of the cross-resistance to cisplatin (CPt) and temozolomide (TMZ) in newly established RC6 cell line, we examined cell death induction and DNA damage by these drugs. Resistance to apoptosis and deficiency in forming DNA double-strand breaks was followed by significant decrease in the mRNA expression of pro-apoptotic and anti-apoptotic genes. The development of drug resistance was associated with significant increase in reactive oxygen species (ROS) and decrease in oxidized to reduced gluthatione ratio in RC6 cell line indicating a reduced level of oxidative stress. The mRNA expression levels of manganese superoxid dismutase (MnSOD), inducible nitric oxide synthase (iNOS) and gluthatione peroxidase (GPx) were increased while hypoxia-inducible factor 1-alpha (HIF-1 alpha) was decreased in RC6 compared to C6 cells. This was in line with obtained changes in ROS content and increased antioxidative capacity of RC6 cells. Importantly, RC6 cells demonstrated collateral sensitivity to doxorubicin (DOX). The analysis of this phenomenon revealed increased accumulation of DOX in RC6 cells due to their adaptation to high ROS content and acidification of cytoplasm. In conclusion, newly established RC6 rat glioma cell line could be used as a starting material for the development of allogenic animal model and preclinical evaluation of new antiglioma agents. Collateral sensitivity to DOX obtained after BCNU treatment may prompt new studies aimed to find efficient delivery of DOX to the glioma site in brain.
PB  - Elsevier Inc.
T2  - Experimental Cell Research
T1  - Development of resistance to antiglioma agents in rat C6 cells caused collateral sensitivity to doxorubicin
IS  - 2
VL  - 335
DO  - 10.1016/j.yexcr.2015.05.018
SP  - 248
EP  - 257
ER  - 

@article{
author = "Stojković Burić, Sonja and Podolski-Renić, Ana and Dinić, Jelena and Stanković, Tijana and Banković, Jasna Z. and Hadzic, Stefan and Paunovic, Verica and Isakovic, Aleksandra and Tanić, Nikola and Pešić, Milica",
year = "2015",
abstract = "Chemoresistance is a severe limitation to glioblastoma (GBM) therapy and there is a strong need to understand the underlying mechanisms that determine its response to different chemotherapeutics. Therefore, we induced resistance in C6 rat glioma cell line, which considerably resembles the characteristics of human GBM. The resistant phenotype was developed by 3-bis (2-chloroethyl)-1-nitrosourea (BCNU), one of the most commonly used therapeutic drug in the course of GBM treatment. After confirmation of the cross-resistance to cisplatin (CPt) and temozolomide (TMZ) in newly established RC6 cell line, we examined cell death induction and DNA damage by these drugs. Resistance to apoptosis and deficiency in forming DNA double-strand breaks was followed by significant decrease in the mRNA expression of pro-apoptotic and anti-apoptotic genes. The development of drug resistance was associated with significant increase in reactive oxygen species (ROS) and decrease in oxidized to reduced gluthatione ratio in RC6 cell line indicating a reduced level of oxidative stress. The mRNA expression levels of manganese superoxid dismutase (MnSOD), inducible nitric oxide synthase (iNOS) and gluthatione peroxidase (GPx) were increased while hypoxia-inducible factor 1-alpha (HIF-1 alpha) was decreased in RC6 compared to C6 cells. This was in line with obtained changes in ROS content and increased antioxidative capacity of RC6 cells. Importantly, RC6 cells demonstrated collateral sensitivity to doxorubicin (DOX). The analysis of this phenomenon revealed increased accumulation of DOX in RC6 cells due to their adaptation to high ROS content and acidification of cytoplasm. In conclusion, newly established RC6 rat glioma cell line could be used as a starting material for the development of allogenic animal model and preclinical evaluation of new antiglioma agents. Collateral sensitivity to DOX obtained after BCNU treatment may prompt new studies aimed to find efficient delivery of DOX to the glioma site in brain.",
publisher = "Elsevier Inc.",
journal = "Experimental Cell Research",
title = "Development of resistance to antiglioma agents in rat C6 cells caused collateral sensitivity to doxorubicin",
number = "2",
volume = "335",
doi = "10.1016/j.yexcr.2015.05.018",
pages = "248-257"
}

Stojković Burić, S., Podolski-Renić, A., Dinić, J., Stanković, T., Banković, J. Z., Hadzic, S., Paunovic, V., Isakovic, A., Tanić, N.,& Pešić, M.. (2015). Development of resistance to antiglioma agents in rat C6 cells caused collateral sensitivity to doxorubicin. in Experimental Cell Research
Elsevier Inc.., 335(2), 248-257.
https://doi.org/10.1016/j.yexcr.2015.05.018

Stojković Burić S, Podolski-Renić A, Dinić J, Stanković T, Banković JZ, Hadzic S, Paunovic V, Isakovic A, Tanić N, Pešić M. Development of resistance to antiglioma agents in rat C6 cells caused collateral sensitivity to doxorubicin. in Experimental Cell Research. 2015;335(2):248-257.
doi:10.1016/j.yexcr.2015.05.018 .

Stojković Burić, Sonja, Podolski-Renić, Ana, Dinić, Jelena, Stanković, Tijana, Banković, Jasna Z., Hadzic, Stefan, Paunovic, Verica, Isakovic, Aleksandra, Tanić, Nikola, Pešić, Milica, "Development of resistance to antiglioma agents in rat C6 cells caused collateral sensitivity to doxorubicin" in Experimental Cell Research, 335, no. 2 (2015):248-257,
https://doi.org/10.1016/j.yexcr.2015.05.018 . .

TY  - JOUR
AU  - Stojković Burić, Sonja
AU  - Podolski-Renić, Ana
AU  - Dinić, Jelena
AU  - Stankovic, Tijana
AU  - Banković, Jasna Z.
AU  - Hadzic, Stefan
AU  - Paunovic, Verica
AU  - Isakovic, Aleksandra
AU  - Tanić, Nikola
AU  - Pešić, Milica
PY  - 2015
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/1926
AB  - Chemoresistance is a severe limitation to glioblastoma (GBM) therapy and
   there is a strong need to understand the underlying mechanisms that
   determine its response to different chemotherapeutics. Therefore, we
   induced resistance in C6 rat glioma cell line, which considerably
   resembles the characteristics of human GBM. The resistant phenotype was
   developed by 3-bis (2-chloroethyl)-1-nitrosourea (BCNU), one of the most
   commonly used therapeutic drug in the course of GBM treatment. After
   confirmation of the cross-resistance to cisplatin (CPt) and temozolomide
   (TMZ) in newly established RC6 cell line, we examined cell death
   induction and DNA damage by these drugs. Resistance to apoptosis and
   deficiency in forming DNA double-strand breaks was followed by
   significant decrease in the mRNA expression of pro-apoptotic and
   anti-apoptotic genes. The development of drug resistance was associated
   with significant increase in reactive oxygen species (ROS) and decrease
   in oxidized to reduced gluthatione ratio in RC6 cell line indicating a
   reduced level of oxidative stress. The mRNA expression levels of
   manganese superoxid dismutase (MnSOD), inducible nitric oxide synthase
   (iNOS) and gluthatione peroxidase (GPx) were increased while
   hypoxia-inducible factor 1-alpha (HIF-1 alpha) was decreased in RC6
   compared to C6 cells. This was in line with obtained changes in ROS
   content and increased antioxidative capacity of RC6 cells. Importantly,
   RC6 cells demonstrated collateral sensitivity to doxorubicin (DOX). The
   analysis of this phenomenon revealed increased accumulation of DOX in
   RC6 cells due to their adaptation to high ROS content and acidification
   of cytoplasm. In conclusion, newly established RC6 rat glioma cell line
   could be used as a starting material for the development of allogenic
   animal model and preclinical evaluation of new antiglioma agents.
   Collateral sensitivity to DOX obtained after BCNU treatment may prompt
   new studies aimed to find efficient delivery of DOX to the glioma site
   in brain. (C) 2015 Elsevier Inc. All rights reserved.
T2  - Experimental Cell Research
T1  - Development of resistance to antiglioma agents in rat C6 cells caused
 collateral sensitivity to doxorubicin
IS  - 2
VL  - 335
DO  - 10.1016/j.yexcr.2015.05.018
SP  - 248
EP  - 257
ER  - 

@article{
author = "Stojković Burić, Sonja and Podolski-Renić, Ana and Dinić, Jelena and Stankovic, Tijana and Banković, Jasna Z. and Hadzic, Stefan and Paunovic, Verica and Isakovic, Aleksandra and Tanić, Nikola and Pešić, Milica",
year = "2015",
abstract = "Chemoresistance is a severe limitation to glioblastoma (GBM) therapy and
   there is a strong need to understand the underlying mechanisms that
   determine its response to different chemotherapeutics. Therefore, we
   induced resistance in C6 rat glioma cell line, which considerably
   resembles the characteristics of human GBM. The resistant phenotype was
   developed by 3-bis (2-chloroethyl)-1-nitrosourea (BCNU), one of the most
   commonly used therapeutic drug in the course of GBM treatment. After
   confirmation of the cross-resistance to cisplatin (CPt) and temozolomide
   (TMZ) in newly established RC6 cell line, we examined cell death
   induction and DNA damage by these drugs. Resistance to apoptosis and
   deficiency in forming DNA double-strand breaks was followed by
   significant decrease in the mRNA expression of pro-apoptotic and
   anti-apoptotic genes. The development of drug resistance was associated
   with significant increase in reactive oxygen species (ROS) and decrease
   in oxidized to reduced gluthatione ratio in RC6 cell line indicating a
   reduced level of oxidative stress. The mRNA expression levels of
   manganese superoxid dismutase (MnSOD), inducible nitric oxide synthase
   (iNOS) and gluthatione peroxidase (GPx) were increased while
   hypoxia-inducible factor 1-alpha (HIF-1 alpha) was decreased in RC6
   compared to C6 cells. This was in line with obtained changes in ROS
   content and increased antioxidative capacity of RC6 cells. Importantly,
   RC6 cells demonstrated collateral sensitivity to doxorubicin (DOX). The
   analysis of this phenomenon revealed increased accumulation of DOX in
   RC6 cells due to their adaptation to high ROS content and acidification
   of cytoplasm. In conclusion, newly established RC6 rat glioma cell line
   could be used as a starting material for the development of allogenic
   animal model and preclinical evaluation of new antiglioma agents.
   Collateral sensitivity to DOX obtained after BCNU treatment may prompt
   new studies aimed to find efficient delivery of DOX to the glioma site
   in brain. (C) 2015 Elsevier Inc. All rights reserved.",
journal = "Experimental Cell Research",
title = "Development of resistance to antiglioma agents in rat C6 cells caused
 collateral sensitivity to doxorubicin",
number = "2",
volume = "335",
doi = "10.1016/j.yexcr.2015.05.018",
pages = "248-257"
}

Stojković Burić, S., Podolski-Renić, A., Dinić, J., Stankovic, T., Banković, J. Z., Hadzic, S., Paunovic, V., Isakovic, A., Tanić, N.,& Pešić, M.. (2015). Development of resistance to antiglioma agents in rat C6 cells caused
 collateral sensitivity to doxorubicin. in Experimental Cell Research, 335(2), 248-257.
https://doi.org/10.1016/j.yexcr.2015.05.018

Stojković Burić S, Podolski-Renić A, Dinić J, Stankovic T, Banković JZ, Hadzic S, Paunovic V, Isakovic A, Tanić N, Pešić M. Development of resistance to antiglioma agents in rat C6 cells caused
 collateral sensitivity to doxorubicin. in Experimental Cell Research. 2015;335(2):248-257.
doi:10.1016/j.yexcr.2015.05.018 .

Stojković Burić, Sonja, Podolski-Renić, Ana, Dinić, Jelena, Stankovic, Tijana, Banković, Jasna Z., Hadzic, Stefan, Paunovic, Verica, Isakovic, Aleksandra, Tanić, Nikola, Pešić, Milica, "Development of resistance to antiglioma agents in rat C6 cells caused
 collateral sensitivity to doxorubicin" in Experimental Cell Research, 335, no. 2 (2015):248-257,
https://doi.org/10.1016/j.yexcr.2015.05.018 . .