TY  - JOUR
AU  - Babić, Tamara
AU  - Dinić, Jelena
AU  - Stojković Burić, Sonja
AU  - Hadzic, Stefan
AU  - Pešić, Milica
AU  - Radojković, Dragica
AU  - Divac Rankov, Aleksandra
PY  - 2018
UR  - https://akjournals.com/view/journals/018/69/4/article-p395.xml
UR  - https://radar.ibiss.bg.ac.rs/123456789/3881
AB  - Cancer drug resistance and poor selectivity towards cancer cells demand the constant search for new therapeutics. PI3K-Akt-mTOR and RAS-MAPK-ERK signaling pathways are key mechanisms involved in cell survival, proliferation, differentiation, and metabolism and their deregulation in cancer can promote development of therapy resistance. We investigated the effects of targeted inhibitors (wortmannin, GSK690693, AZD2014 and tipifarnib) towards these two pathways on early zebrafish and sea urchin development to assess their toxicity in normal, fast proliferating cells. PI3K inhibitor wortmannin and RAS inhibitor tipifarnib displayed highest toxicity while GSK690693, a pan-Akt kinase inhibitor, exhibited a less significant impact on embryo survival and development. Moreover, inhibition of the upstream part of the PI3K-Akt-mTOR pathway (wortmannin/GSK690693 co-treatment) produced a synergistic effect and impacted zebrafish embryo survival and development at much lower concentrations. Dual mTORC1/mTORC2 inhibitor AZD2014 showed no considerable effects on embryonic cells of zebrafish in concentrations substantially toxic in cancer cells. AZD2014 also caused the least prominent effects on sea urchin embryo development compared to other inhibitors. Significant toxicity of AZD2014 in human cancer cells, its capacity to sensitize resistant cancers, lower antiproliferative activity against human normal cell lines and fast proliferating embryonic cells could make this agent a promising candidate for anticancer therapy.
PB  - Budapest : Akadémiai Kiadó
T2  - Acta Biologica Hungarica
T1  - Comparative toxicity evaluation of targeted anticancer therapeutics in embryonic zebrafish and sea urchin models
IS  - 4
VL  - 69
DO  - 10.1556/018.69.2018.4.3
SP  - 395
EP  - 410
ER  - 

@article{
author = "Babić, Tamara and Dinić, Jelena and Stojković Burić, Sonja and Hadzic, Stefan and Pešić, Milica and Radojković, Dragica and Divac Rankov, Aleksandra",
year = "2018",
abstract = "Cancer drug resistance and poor selectivity towards cancer cells demand the constant search for new therapeutics. PI3K-Akt-mTOR and RAS-MAPK-ERK signaling pathways are key mechanisms involved in cell survival, proliferation, differentiation, and metabolism and their deregulation in cancer can promote development of therapy resistance. We investigated the effects of targeted inhibitors (wortmannin, GSK690693, AZD2014 and tipifarnib) towards these two pathways on early zebrafish and sea urchin development to assess their toxicity in normal, fast proliferating cells. PI3K inhibitor wortmannin and RAS inhibitor tipifarnib displayed highest toxicity while GSK690693, a pan-Akt kinase inhibitor, exhibited a less significant impact on embryo survival and development. Moreover, inhibition of the upstream part of the PI3K-Akt-mTOR pathway (wortmannin/GSK690693 co-treatment) produced a synergistic effect and impacted zebrafish embryo survival and development at much lower concentrations. Dual mTORC1/mTORC2 inhibitor AZD2014 showed no considerable effects on embryonic cells of zebrafish in concentrations substantially toxic in cancer cells. AZD2014 also caused the least prominent effects on sea urchin embryo development compared to other inhibitors. Significant toxicity of AZD2014 in human cancer cells, its capacity to sensitize resistant cancers, lower antiproliferative activity against human normal cell lines and fast proliferating embryonic cells could make this agent a promising candidate for anticancer therapy.",
publisher = "Budapest : Akadémiai Kiadó",
journal = "Acta Biologica Hungarica",
title = "Comparative toxicity evaluation of targeted anticancer therapeutics in embryonic zebrafish and sea urchin models",
number = "4",
volume = "69",
doi = "10.1556/018.69.2018.4.3",
pages = "395-410"
}

Babić, T., Dinić, J., Stojković Burić, S., Hadzic, S., Pešić, M., Radojković, D.,& Divac Rankov, A.. (2018). Comparative toxicity evaluation of targeted anticancer therapeutics in embryonic zebrafish and sea urchin models. in Acta Biologica Hungarica
Budapest : Akadémiai Kiadó., 69(4), 395-410.
https://doi.org/10.1556/018.69.2018.4.3

Babić T, Dinić J, Stojković Burić S, Hadzic S, Pešić M, Radojković D, Divac Rankov A. Comparative toxicity evaluation of targeted anticancer therapeutics in embryonic zebrafish and sea urchin models. in Acta Biologica Hungarica. 2018;69(4):395-410.
doi:10.1556/018.69.2018.4.3 .

Babić, Tamara, Dinić, Jelena, Stojković Burić, Sonja, Hadzic, Stefan, Pešić, Milica, Radojković, Dragica, Divac Rankov, Aleksandra, "Comparative toxicity evaluation of targeted anticancer therapeutics in embryonic zebrafish and sea urchin models" in Acta Biologica Hungarica, 69, no. 4 (2018):395-410,
https://doi.org/10.1556/018.69.2018.4.3 . .

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 . .