TY  - CONF
AU  - Misirkić Marjanović, Maja
AU  - Vučićević, Ljubica
AU  - Ćirić, Darko
AU  - Martinović, Tamara
AU  - Jovanović, Maja
AU  - Isaković, Aleksandra
AU  - Marković, Ivanka
AU  - Trajković, Vladimir
PY  - 2019
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6661
AB  - We investigated the role of autophagy in glutamate excitotoxicity during nutrient deprivation in vitro. Lack of serum, amino acids, and glucose markedly increased the sensitivity of SH-SY5Y human neuroblastoma cell line to glutamate-induced excitotoxic necrosis. Glutamate suppressed starvation-triggered autophagic response, as confirmed by diminished intracellular acidification, lower LC3 punctuation and conversion of LC3I to autophagosome associated LC3II, reduced levels of autophagy activators beclin-1 and ATG5, increased levels of the selective autophagic target NBR1, and reduced appearance of autophagic vesicles observed by transmission electron microscopy. Glutamate reduced starvation-triggered phosphorylation of the intracellular energy sensor AMP-activated protein kinase (AMPK), without affecting the activity of mammalian target of rapamycin complex1 as a major negative regulator of autophagy. Similar results were shown on PC12 cells, which are often exploited as a model for excitotoxicity. We also detected reduced mRNA expression of autophagy transcription factors FOXO3 and ATF4, as well as molecules involved in autophagy initiation (ULK1, ATG13, FIP200), autophagosome nucleation/elongation (ATG14, beclin 1, ATG5, ATG12), and the autophagy cargo delivery to autophagosmes (SQSTM1/p62). Genetic or pharmacological AMPK activation by AMPK overexpression or metformin, reduced the sensitivity of nutrient-deprived SH-SY5Y cells to glutamate dependent autophagy is involved in glutamate-mediated excitotoxicity during nutrient deprivation in vitro.
PB  - Nordic Autophagy Society
C3  - 3rd Nordic Autophagy Society (NAS) Conference; 2019 May 22-24; Utrecht, Nederlands
T1  - Glutamate-mediated autophagy inhibition intensifies excitotoxic death of nutrient-deprived SH-SY5Y neuroblastoma cells
SP  - 34
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_6661
ER  - 

@conference{
author = "Misirkić Marjanović, Maja and Vučićević, Ljubica and Ćirić, Darko and Martinović, Tamara and Jovanović, Maja and Isaković, Aleksandra and Marković, Ivanka and Trajković, Vladimir",
year = "2019",
abstract = "We investigated the role of autophagy in glutamate excitotoxicity during nutrient deprivation in vitro. Lack of serum, amino acids, and glucose markedly increased the sensitivity of SH-SY5Y human neuroblastoma cell line to glutamate-induced excitotoxic necrosis. Glutamate suppressed starvation-triggered autophagic response, as confirmed by diminished intracellular acidification, lower LC3 punctuation and conversion of LC3I to autophagosome associated LC3II, reduced levels of autophagy activators beclin-1 and ATG5, increased levels of the selective autophagic target NBR1, and reduced appearance of autophagic vesicles observed by transmission electron microscopy. Glutamate reduced starvation-triggered phosphorylation of the intracellular energy sensor AMP-activated protein kinase (AMPK), without affecting the activity of mammalian target of rapamycin complex1 as a major negative regulator of autophagy. Similar results were shown on PC12 cells, which are often exploited as a model for excitotoxicity. We also detected reduced mRNA expression of autophagy transcription factors FOXO3 and ATF4, as well as molecules involved in autophagy initiation (ULK1, ATG13, FIP200), autophagosome nucleation/elongation (ATG14, beclin 1, ATG5, ATG12), and the autophagy cargo delivery to autophagosmes (SQSTM1/p62). Genetic or pharmacological AMPK activation by AMPK overexpression or metformin, reduced the sensitivity of nutrient-deprived SH-SY5Y cells to glutamate dependent autophagy is involved in glutamate-mediated excitotoxicity during nutrient deprivation in vitro.",
publisher = "Nordic Autophagy Society",
journal = "3rd Nordic Autophagy Society (NAS) Conference; 2019 May 22-24; Utrecht, Nederlands",
title = "Glutamate-mediated autophagy inhibition intensifies excitotoxic death of nutrient-deprived SH-SY5Y neuroblastoma cells",
pages = "34",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_6661"
}

Misirkić Marjanović, M., Vučićević, L., Ćirić, D., Martinović, T., Jovanović, M., Isaković, A., Marković, I.,& Trajković, V.. (2019). Glutamate-mediated autophagy inhibition intensifies excitotoxic death of nutrient-deprived SH-SY5Y neuroblastoma cells. in 3rd Nordic Autophagy Society (NAS) Conference; 2019 May 22-24; Utrecht, Nederlands
Nordic Autophagy Society., 34.
https://hdl.handle.net/21.15107/rcub_ibiss_6661

Misirkić Marjanović M, Vučićević L, Ćirić D, Martinović T, Jovanović M, Isaković A, Marković I, Trajković V. Glutamate-mediated autophagy inhibition intensifies excitotoxic death of nutrient-deprived SH-SY5Y neuroblastoma cells. in 3rd Nordic Autophagy Society (NAS) Conference; 2019 May 22-24; Utrecht, Nederlands. 2019;:34.
https://hdl.handle.net/21.15107/rcub_ibiss_6661 .

Misirkić Marjanović, Maja, Vučićević, Ljubica, Ćirić, Darko, Martinović, Tamara, Jovanović, Maja, Isaković, Aleksandra, Marković, Ivanka, Trajković, Vladimir, "Glutamate-mediated autophagy inhibition intensifies excitotoxic death of nutrient-deprived SH-SY5Y neuroblastoma cells" in 3rd Nordic Autophagy Society (NAS) Conference; 2019 May 22-24; Utrecht, Nederlands (2019):34,
https://hdl.handle.net/21.15107/rcub_ibiss_6661 .

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 . .

TY  - JOUR
AU  - Isaković, Aleksandra
AU  - Harhaji-Trajković, Ljubica
AU  - Dacević, Mirjana
AU  - Trajković, Vladimir
PY  - 2008
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6546
AB  - We investigated the influence of adenosine on inducible nitric oxide (NO) synthase (iNOS)-dependent NO synthesis and viability of cytokine-treated C6 rat glioma cells. Adenosine significantly inhibited interferon-gamma (IFN-gamma)+interleukin-1beta (IL-1beta)-induced synthesis of iNOS mRNA/protein and subsequent production of NO in C6 cells. The uptake of adenosine into glioma cells was not required for the suppression of iNOS induction, as confirmed by the inability of the adenosine transport blocker nitrobenzylthyoinosine to block the observed effect. Adenosine also blocked the IFN-gamma+IL-1beta-triggered expression of mRNA for the proinflammatory cytokine TNF-alpha, while it significantly enhanced the accumulation of cyclooxygenase-2 (COX-2) mRNA in glioma cells. However, blockade of TNF-alpha action and COX-2 activity with anti-TNF-alpha antibodies and indomethacin, respectively, revealed that modulation of TNF-alpha and COX-2 was not involved in adenosine-mediated iNOS suppression. Adenosine significantly inhibited cytokine-induced activation of mitogen-activated protein kinase (MAPK) family members p38 MAPK, p42/44 MAPK and c-Jun N-terminal kinase (JNK) in C6 cells. The levels of transcription factors IRF-1 and c-Fos, as well as the phosphorylation of c-Jun were also reduced in adenosine-treated C6 cells, while the activation of NF-kappaB was enhanced via increased phosphorylation of its inhibitory unit IkappaB. Importantly, adenosine-mediated suppression of NO release rescued glioma cells from NO-dependent cytokine cytotoxicity. These data suggest a possible role for adenosine-mediated inhibition of glial NO synthesis in regulation of the inflammatory CNS damage and brain cancer progression.
PB  - Elsevier BV
T2  - European Journal of Pharmacology
T1  - Adenosine rescues glioma cells from cytokine-induced death by interfering with the signaling network involved in nitric oxide production
IS  - 1-3
VL  - 591
DO  - 10.1016/j.ejphar.2008.06.076
SP  - 106
EP  - 113
ER  - 

@article{
author = "Isaković, Aleksandra and Harhaji-Trajković, Ljubica and Dacević, Mirjana and Trajković, Vladimir",
year = "2008",
abstract = "We investigated the influence of adenosine on inducible nitric oxide (NO) synthase (iNOS)-dependent NO synthesis and viability of cytokine-treated C6 rat glioma cells. Adenosine significantly inhibited interferon-gamma (IFN-gamma)+interleukin-1beta (IL-1beta)-induced synthesis of iNOS mRNA/protein and subsequent production of NO in C6 cells. The uptake of adenosine into glioma cells was not required for the suppression of iNOS induction, as confirmed by the inability of the adenosine transport blocker nitrobenzylthyoinosine to block the observed effect. Adenosine also blocked the IFN-gamma+IL-1beta-triggered expression of mRNA for the proinflammatory cytokine TNF-alpha, while it significantly enhanced the accumulation of cyclooxygenase-2 (COX-2) mRNA in glioma cells. However, blockade of TNF-alpha action and COX-2 activity with anti-TNF-alpha antibodies and indomethacin, respectively, revealed that modulation of TNF-alpha and COX-2 was not involved in adenosine-mediated iNOS suppression. Adenosine significantly inhibited cytokine-induced activation of mitogen-activated protein kinase (MAPK) family members p38 MAPK, p42/44 MAPK and c-Jun N-terminal kinase (JNK) in C6 cells. The levels of transcription factors IRF-1 and c-Fos, as well as the phosphorylation of c-Jun were also reduced in adenosine-treated C6 cells, while the activation of NF-kappaB was enhanced via increased phosphorylation of its inhibitory unit IkappaB. Importantly, adenosine-mediated suppression of NO release rescued glioma cells from NO-dependent cytokine cytotoxicity. These data suggest a possible role for adenosine-mediated inhibition of glial NO synthesis in regulation of the inflammatory CNS damage and brain cancer progression.",
publisher = "Elsevier BV",
journal = "European Journal of Pharmacology",
title = "Adenosine rescues glioma cells from cytokine-induced death by interfering with the signaling network involved in nitric oxide production",
number = "1-3",
volume = "591",
doi = "10.1016/j.ejphar.2008.06.076",
pages = "106-113"
}

Isaković, A., Harhaji-Trajković, L., Dacević, M.,& Trajković, V.. (2008). Adenosine rescues glioma cells from cytokine-induced death by interfering with the signaling network involved in nitric oxide production. in European Journal of Pharmacology
Elsevier BV., 591(1-3), 106-113.
https://doi.org/10.1016/j.ejphar.2008.06.076

Isaković A, Harhaji-Trajković L, Dacević M, Trajković V. Adenosine rescues glioma cells from cytokine-induced death by interfering with the signaling network involved in nitric oxide production. in European Journal of Pharmacology. 2008;591(1-3):106-113.
doi:10.1016/j.ejphar.2008.06.076 .

Isaković, Aleksandra, Harhaji-Trajković, Ljubica, Dacević, Mirjana, Trajković, Vladimir, "Adenosine rescues glioma cells from cytokine-induced death by interfering with the signaling network involved in nitric oxide production" in European Journal of Pharmacology, 591, no. 1-3 (2008):106-113,
https://doi.org/10.1016/j.ejphar.2008.06.076 . .

TY  - JOUR
AU  - Harhaji-Trajković, Ljubica
AU  - Isaković, Aleksandra
AU  - Zogović, Nevena
AU  - Marković, Zoran
AU  - Todorović-Marković, Biljana
AU  - Nikolić, Nadežda
AU  - Vranješ-Đurić, Sanja
AU  - Marković, Ivanka
AU  - Trajković, Vladimir
PY  - 2007
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6544
AB  - Using the rat glioma cell line C6 and the human glioma cell line U251, we demonstrate the multiple mechanisms underlying the in vitro anticancer effects of the C(60) fullerene water suspension (nano-C(60) or nC(60)) produced by solvent exchange method. Nano-C(60) in a dose-dependent manner reduced the tumor cell numbers after 24 h of incubation. The observed antiglioma action of nC(60) at high concentration (1 microg/ml) was due to a reactive oxygen species-mediated necrotic cell damage that was partly dependent on oxidative stress-induced activation of extracellular signal-regulated kinase (ERK). On the other hand, low-dose nC(60) (0.25 microg/ml) did not induce either necrotic or apoptotic cell death, but caused oxidative stress/ERK-independent cell cycle block in G(2)/M phase and subsequent inhibition of tumor cell proliferation. Treatment with either high-dose or low-dose nC(60) caused the appearance of acidified intracytoplasmic vesicles indicative of autophagy, but only the antiglioma effect of low-dose nC(60) was significantly attenuated by inhibiting autophagy with bafilomycin A1. Importantly, primary rat astrocytes were less sensitive than their transformed counterparts to a cytostatic action of low-dose nC(60). These data provide grounds for further development of nC(60) as an anticancer agent.
PB  - Elsevier BV
T2  - European Journal of Pharmacology
T1  - Multiple mechanisms underlying the anticancer action of nanocrystalline fullerene
IS  - 1-3
VL  - 568
DO  - 10.1016/j.ejphar.2007.04.041
SP  - 89
EP  - 98
ER  - 

@article{
author = "Harhaji-Trajković, Ljubica and Isaković, Aleksandra and Zogović, Nevena and Marković, Zoran and Todorović-Marković, Biljana and Nikolić, Nadežda and Vranješ-Đurić, Sanja and Marković, Ivanka and Trajković, Vladimir",
year = "2007",
abstract = "Using the rat glioma cell line C6 and the human glioma cell line U251, we demonstrate the multiple mechanisms underlying the in vitro anticancer effects of the C(60) fullerene water suspension (nano-C(60) or nC(60)) produced by solvent exchange method. Nano-C(60) in a dose-dependent manner reduced the tumor cell numbers after 24 h of incubation. The observed antiglioma action of nC(60) at high concentration (1 microg/ml) was due to a reactive oxygen species-mediated necrotic cell damage that was partly dependent on oxidative stress-induced activation of extracellular signal-regulated kinase (ERK). On the other hand, low-dose nC(60) (0.25 microg/ml) did not induce either necrotic or apoptotic cell death, but caused oxidative stress/ERK-independent cell cycle block in G(2)/M phase and subsequent inhibition of tumor cell proliferation. Treatment with either high-dose or low-dose nC(60) caused the appearance of acidified intracytoplasmic vesicles indicative of autophagy, but only the antiglioma effect of low-dose nC(60) was significantly attenuated by inhibiting autophagy with bafilomycin A1. Importantly, primary rat astrocytes were less sensitive than their transformed counterparts to a cytostatic action of low-dose nC(60). These data provide grounds for further development of nC(60) as an anticancer agent.",
publisher = "Elsevier BV",
journal = "European Journal of Pharmacology",
title = "Multiple mechanisms underlying the anticancer action of nanocrystalline fullerene",
number = "1-3",
volume = "568",
doi = "10.1016/j.ejphar.2007.04.041",
pages = "89-98"
}

Harhaji-Trajković, L., Isaković, A., Zogović, N., Marković, Z., Todorović-Marković, B., Nikolić, N., Vranješ-Đurić, S., Marković, I.,& Trajković, V.. (2007). Multiple mechanisms underlying the anticancer action of nanocrystalline fullerene. in European Journal of Pharmacology
Elsevier BV., 568(1-3), 89-98.
https://doi.org/10.1016/j.ejphar.2007.04.041

Harhaji-Trajković L, Isaković A, Zogović N, Marković Z, Todorović-Marković B, Nikolić N, Vranješ-Đurić S, Marković I, Trajković V. Multiple mechanisms underlying the anticancer action of nanocrystalline fullerene. in European Journal of Pharmacology. 2007;568(1-3):89-98.
doi:10.1016/j.ejphar.2007.04.041 .

Harhaji-Trajković, Ljubica, Isaković, Aleksandra, Zogović, Nevena, Marković, Zoran, Todorović-Marković, Biljana, Nikolić, Nadežda, Vranješ-Đurić, Sanja, Marković, Ivanka, Trajković, Vladimir, "Multiple mechanisms underlying the anticancer action of nanocrystalline fullerene" in European Journal of Pharmacology, 568, no. 1-3 (2007):89-98,
https://doi.org/10.1016/j.ejphar.2007.04.041 . .

TY  - JOUR
AU  - Harhaji-Trajković, Ljubica
AU  - Mijatović, Sanja
AU  - Maksimović-Ivanić, Danijela
AU  - Popadić, Dusan
AU  - Isaković,  Aleksandra
AU  - Todorović-Marković, Biljana
AU  - Trajković, Vladimir
PY  - 2007
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3825
AB  - We demonstrate the capacity of an herbal anthraquinone aloe emodin to reduce the cytotoxicity of the proinflammatory cytokine tumor necrosis factor (TNF) towards L929 mouse fibrosarcoma and U251 human glioma cell lines. Aloe emodin inhibited both TNF-induced cell necrosis and apoptosis, but it did not reduce cell death induced by UV radiation or hydrogen peroxide. Aloe emodin inhibited both basal and TNF-triggered activation of extracellular signal-regulated kinase (ERK), and a selective blockade of ERK activation mimicked the cytoprotective action of the drug. On the other hand, aloe emodin did not affect TNF-induced activation of p38 mitogen-activated protein kinase or generation of reactive oxygen species. The combination of aloe emodin and TNF caused an intracellular appearance of acidified autophagic vesicles, and the inhibition of autophagy with bafilomycin or 3-methyladenine efficiently blocked the cytoprotective action of aloe emodin. These data indicate that aloe emodin could prevent TNF-triggered cell death through mechanisms involving induction of autophagy and blockade of ERK activation.
PB  - Amsterdam: Elsevier
T2  - European Journal of Pharmacology
T1  - Aloe emodin inhibits the cytotoxic action of tumor necrosis factor
IS  - 1-3
VL  - 568
VL  - 568
DO  - 10.1016/j.ejphar.2007.04.029
SP  - 248
EP  - 259
ER  - 

@article{
author = "Harhaji-Trajković, Ljubica and Mijatović, Sanja and Maksimović-Ivanić, Danijela and Popadić, Dusan and Isaković,  Aleksandra and Todorović-Marković, Biljana and Trajković, Vladimir",
year = "2007",
abstract = "We demonstrate the capacity of an herbal anthraquinone aloe emodin to reduce the cytotoxicity of the proinflammatory cytokine tumor necrosis factor (TNF) towards L929 mouse fibrosarcoma and U251 human glioma cell lines. Aloe emodin inhibited both TNF-induced cell necrosis and apoptosis, but it did not reduce cell death induced by UV radiation or hydrogen peroxide. Aloe emodin inhibited both basal and TNF-triggered activation of extracellular signal-regulated kinase (ERK), and a selective blockade of ERK activation mimicked the cytoprotective action of the drug. On the other hand, aloe emodin did not affect TNF-induced activation of p38 mitogen-activated protein kinase or generation of reactive oxygen species. The combination of aloe emodin and TNF caused an intracellular appearance of acidified autophagic vesicles, and the inhibition of autophagy with bafilomycin or 3-methyladenine efficiently blocked the cytoprotective action of aloe emodin. These data indicate that aloe emodin could prevent TNF-triggered cell death through mechanisms involving induction of autophagy and blockade of ERK activation.",
publisher = "Amsterdam: Elsevier",
journal = "European Journal of Pharmacology",
title = "Aloe emodin inhibits the cytotoxic action of tumor necrosis factor",
number = "1-3",
volume = "568, 568",
doi = "10.1016/j.ejphar.2007.04.029",
pages = "248-259"
}

Harhaji-Trajković, L., Mijatović, S., Maksimović-Ivanić, D., Popadić, D., Isaković,  ., Todorović-Marković, B.,& Trajković, V.. (2007). Aloe emodin inhibits the cytotoxic action of tumor necrosis factor. in European Journal of Pharmacology
Amsterdam: Elsevier., 568(1-3), 248-259.
https://doi.org/10.1016/j.ejphar.2007.04.029

Harhaji-Trajković L, Mijatović S, Maksimović-Ivanić D, Popadić D, Isaković  , Todorović-Marković B, Trajković V. Aloe emodin inhibits the cytotoxic action of tumor necrosis factor. in European Journal of Pharmacology. 2007;568(1-3):248-259.
doi:10.1016/j.ejphar.2007.04.029 .

Harhaji-Trajković, Ljubica, Mijatović, Sanja, Maksimović-Ivanić, Danijela, Popadić, Dusan, Isaković,  Aleksandra, Todorović-Marković, Biljana, Trajković, Vladimir, "Aloe emodin inhibits the cytotoxic action of tumor necrosis factor" in European Journal of Pharmacology, 568, no. 1-3 (2007):248-259,
https://doi.org/10.1016/j.ejphar.2007.04.029 . .