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  - Babić, Tamara
AU  - Dinić, Jelena
AU  - Stojković Burić, Sonja
AU  - Hadžić, Stefan
AU  - Pešić, Milica
AU  - Radojković, Dragica
AU  - Divac Rankov, Aleksandra
PY  - 2018
UR  - https://www.akademiai.com/doi/10.1556/018.69.2018.4.3
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3231
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.
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 Hadžić, 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.",
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., Hadžić, 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, 69(4), 395-410.
https://doi.org/10.1556/018.69.2018.4.3

Babić T, Dinić J, Stojković Burić S, Hadžić 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, Hadžić, 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 . .