TY  - JOUR
AU  - Podolski-Renić, Ana
AU  - Banković, Jasna
AU  - Dinić, Jelena
AU  - Ríos-Luci, Carla
AU  - Fernandes, Miguel X.
AU  - Ortega, Nuria
AU  - Kovačević-Grujičić, Nataša
AU  - Martín, Víctor S.
AU  - Padrón, José M.
AU  - Pešić, Milica
PY  - 2017
UR  - https://www.sciencedirect.com/science/article/abs/pii/S0928098717302397
UR  - https://radar.ibiss.bg.ac.rs/123456789/3873
AB  - The efficacy of microtubule targeting agents in cancer treatment has been compromised by the development of drug resistance that may involve both, P-glycoprotein overexpression and the changes in β-tubulin isoforms' expression. The anti-Topoisomerase II activity of methyl 4-((E)-2-(methoxycarbonyl)vinyloxy)oct-2-ynoate (DTA0100) was recently reported. Herein, we further evaluated this propargylic enol ether derivative and found that it exerts inhibitory effect on tubulin polymerization by binding to colchicine binding site. DTA0100 mitotic arrest properties were investigated in two multi-drug resistant cancer cell lines with P-glycoprotein overexpression (colorectal carcinoma and glioblastoma). The sensitivity of multi-drug resistant cancer cell lines to DTA0100 was not significantly changed in contrast to microtubule targeting agents such as paclitaxel, vinblastine and colchicine. DTA0100 clearly induced microtubule depolymerization, leading to disturbance of cell cycle kinetics and subsequent apoptosis. The fine-tuning in β-tubulin isoforms expression observed in multi-drug resistant cancer cells may influence the efficacy of DTA0100. Importantly, DTA0100 blocked the P-glycoprotein function in both multi-drug resistant cancer cell lines without inducing the increase in P-glycoprotein expression. Therefore, DTA0100 acting as dual inhibitor of Topoisomerase II and microtubule formation could be considered as multi-potent anticancer agent. Besides, it is able to overcome the problem of drug resistance that emerges in the therapeutic approaches with either Topoisomerase II or microtubule targeting agents.
PB  - Amsterdam: Elsevier
T2  - European Journal of Pharmaceutical Sciences
T1  - DTA0100, dual topoisomerase II and microtubule inhibitor, evades paclitaxel resistance in P-glycoprotein overexpressing cancer cells
VL  - 105
DO  - 10.1016/j.ejps.2017.05.011
SP  - 159
EP  - 168
ER  - 

@article{
author = "Podolski-Renić, Ana and Banković, Jasna and Dinić, Jelena and Ríos-Luci, Carla and Fernandes, Miguel X. and Ortega, Nuria and Kovačević-Grujičić, Nataša and Martín, Víctor S. and Padrón, José M. and Pešić, Milica",
year = "2017",
abstract = "The efficacy of microtubule targeting agents in cancer treatment has been compromised by the development of drug resistance that may involve both, P-glycoprotein overexpression and the changes in β-tubulin isoforms' expression. The anti-Topoisomerase II activity of methyl 4-((E)-2-(methoxycarbonyl)vinyloxy)oct-2-ynoate (DTA0100) was recently reported. Herein, we further evaluated this propargylic enol ether derivative and found that it exerts inhibitory effect on tubulin polymerization by binding to colchicine binding site. DTA0100 mitotic arrest properties were investigated in two multi-drug resistant cancer cell lines with P-glycoprotein overexpression (colorectal carcinoma and glioblastoma). The sensitivity of multi-drug resistant cancer cell lines to DTA0100 was not significantly changed in contrast to microtubule targeting agents such as paclitaxel, vinblastine and colchicine. DTA0100 clearly induced microtubule depolymerization, leading to disturbance of cell cycle kinetics and subsequent apoptosis. The fine-tuning in β-tubulin isoforms expression observed in multi-drug resistant cancer cells may influence the efficacy of DTA0100. Importantly, DTA0100 blocked the P-glycoprotein function in both multi-drug resistant cancer cell lines without inducing the increase in P-glycoprotein expression. Therefore, DTA0100 acting as dual inhibitor of Topoisomerase II and microtubule formation could be considered as multi-potent anticancer agent. Besides, it is able to overcome the problem of drug resistance that emerges in the therapeutic approaches with either Topoisomerase II or microtubule targeting agents.",
publisher = "Amsterdam: Elsevier",
journal = "European Journal of Pharmaceutical Sciences",
title = "DTA0100, dual topoisomerase II and microtubule inhibitor, evades paclitaxel resistance in P-glycoprotein overexpressing cancer cells",
volume = "105",
doi = "10.1016/j.ejps.2017.05.011",
pages = "159-168"
}

Podolski-Renić, A., Banković, J., Dinić, J., Ríos-Luci, C., Fernandes, M. X., Ortega, N., Kovačević-Grujičić, N., Martín, V. S., Padrón, J. M.,& Pešić, M.. (2017). DTA0100, dual topoisomerase II and microtubule inhibitor, evades paclitaxel resistance in P-glycoprotein overexpressing cancer cells. in European Journal of Pharmaceutical Sciences
Amsterdam: Elsevier., 105, 159-168.
https://doi.org/10.1016/j.ejps.2017.05.011

Podolski-Renić A, Banković J, Dinić J, Ríos-Luci C, Fernandes MX, Ortega N, Kovačević-Grujičić N, Martín VS, Padrón JM, Pešić M. DTA0100, dual topoisomerase II and microtubule inhibitor, evades paclitaxel resistance in P-glycoprotein overexpressing cancer cells. in European Journal of Pharmaceutical Sciences. 2017;105:159-168.
doi:10.1016/j.ejps.2017.05.011 .

Podolski-Renić, Ana, Banković, Jasna, Dinić, Jelena, Ríos-Luci, Carla, Fernandes, Miguel X., Ortega, Nuria, Kovačević-Grujičić, Nataša, Martín, Víctor S., Padrón, José M., Pešić, Milica, "DTA0100, dual topoisomerase II and microtubule inhibitor, evades paclitaxel resistance in P-glycoprotein overexpressing cancer cells" in European Journal of Pharmaceutical Sciences, 105 (2017):159-168,
https://doi.org/10.1016/j.ejps.2017.05.011 . .

TY  - JOUR
AU  - Podolski-Renić, Ana
AU  - Banković, Jasna
AU  - Dinić, Jelena
AU  - Ríos-Luci, Carla
AU  - Fernandes, Miguel X.
AU  - Ortega, Nuria
AU  - Kovačević-Grujičić, Nataša
AU  - Martín, Víctor S.
AU  - Padrón, José M.
AU  - Pešić, Milica
PY  - 2017
UR  - http://linkinghub.elsevier.com/retrieve/pii/S0928098717302397
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/2762
AB  - The efficacy of microtubule targeting agents in cancer treatment has been compromised by the development of drug resistance that may involve both, P-glycoprotein overexpression and the changes in β-tubulin isoforms' expression. The anti-Topoisomerase II activity of methyl 4-((E)-2-(methoxycarbonyl)vinyloxy)oct-2-ynoate (DTA0100) was recently reported. Herein, we further evaluated this propargylic enol ether derivative and found that it exerts inhibitory effect on tubulin polymerization by binding to colchicine binding site. DTA0100 mitotic arrest properties were investigated in two multi-drug resistant cancer cell lines with P-glycoprotein overexpression (colorectal carcinoma and glioblastoma). The sensitivity of multi-drug resistant cancer cell lines to DTA0100 was not significantly changed in contrast to microtubule targeting agents such as paclitaxel, vinblastine and colchicine. DTA0100 clearly induced microtubule depolymerization, leading to disturbance of cell cycle kinetics and subsequent apoptosis. The fine-tuning in β-tubulin isoforms expression observed in multi-drug resistant cancer cells may influence the efficacy of DTA0100. Importantly, DTA0100 blocked the P-glycoprotein function in both multi-drug resistant cancer cell lines without inducing the increase in P-glycoprotein expression. Therefore, DTA0100 acting as dual inhibitor of Topoisomerase II and microtubule formation could be considered as multi-potent anticancer agent. Besides, it is able to overcome the problem of drug resistance that emerges in the therapeutic approaches with either Topoisomerase II or microtubule targeting agents.
T2  - European Journal of Pharmaceutical Sciences
T1  - DTA0100, dual topoisomerase II and microtubule inhibitor, evades paclitaxel resistance in P-glycoprotein overexpressing cancer cells
VL  - 105
DO  - 10.1016/j.ejps.2017.05.011
SP  - 159
EP  - 168
ER  - 

@article{
author = "Podolski-Renić, Ana and Banković, Jasna and Dinić, Jelena and Ríos-Luci, Carla and Fernandes, Miguel X. and Ortega, Nuria and Kovačević-Grujičić, Nataša and Martín, Víctor S. and Padrón, José M. and Pešić, Milica",
year = "2017",
abstract = "The efficacy of microtubule targeting agents in cancer treatment has been compromised by the development of drug resistance that may involve both, P-glycoprotein overexpression and the changes in β-tubulin isoforms' expression. The anti-Topoisomerase II activity of methyl 4-((E)-2-(methoxycarbonyl)vinyloxy)oct-2-ynoate (DTA0100) was recently reported. Herein, we further evaluated this propargylic enol ether derivative and found that it exerts inhibitory effect on tubulin polymerization by binding to colchicine binding site. DTA0100 mitotic arrest properties were investigated in two multi-drug resistant cancer cell lines with P-glycoprotein overexpression (colorectal carcinoma and glioblastoma). The sensitivity of multi-drug resistant cancer cell lines to DTA0100 was not significantly changed in contrast to microtubule targeting agents such as paclitaxel, vinblastine and colchicine. DTA0100 clearly induced microtubule depolymerization, leading to disturbance of cell cycle kinetics and subsequent apoptosis. The fine-tuning in β-tubulin isoforms expression observed in multi-drug resistant cancer cells may influence the efficacy of DTA0100. Importantly, DTA0100 blocked the P-glycoprotein function in both multi-drug resistant cancer cell lines without inducing the increase in P-glycoprotein expression. Therefore, DTA0100 acting as dual inhibitor of Topoisomerase II and microtubule formation could be considered as multi-potent anticancer agent. Besides, it is able to overcome the problem of drug resistance that emerges in the therapeutic approaches with either Topoisomerase II or microtubule targeting agents.",
journal = "European Journal of Pharmaceutical Sciences",
title = "DTA0100, dual topoisomerase II and microtubule inhibitor, evades paclitaxel resistance in P-glycoprotein overexpressing cancer cells",
volume = "105",
doi = "10.1016/j.ejps.2017.05.011",
pages = "159-168"
}

Podolski-Renić, A., Banković, J., Dinić, J., Ríos-Luci, C., Fernandes, M. X., Ortega, N., Kovačević-Grujičić, N., Martín, V. S., Padrón, J. M.,& Pešić, M.. (2017). DTA0100, dual topoisomerase II and microtubule inhibitor, evades paclitaxel resistance in P-glycoprotein overexpressing cancer cells. in European Journal of Pharmaceutical Sciences, 105, 159-168.
https://doi.org/10.1016/j.ejps.2017.05.011

Podolski-Renić A, Banković J, Dinić J, Ríos-Luci C, Fernandes MX, Ortega N, Kovačević-Grujičić N, Martín VS, Padrón JM, Pešić M. DTA0100, dual topoisomerase II and microtubule inhibitor, evades paclitaxel resistance in P-glycoprotein overexpressing cancer cells. in European Journal of Pharmaceutical Sciences. 2017;105:159-168.
doi:10.1016/j.ejps.2017.05.011 .

Podolski-Renić, Ana, Banković, Jasna, Dinić, Jelena, Ríos-Luci, Carla, Fernandes, Miguel X., Ortega, Nuria, Kovačević-Grujičić, Nataša, Martín, Víctor S., Padrón, José M., Pešić, Milica, "DTA0100, dual topoisomerase II and microtubule inhibitor, evades paclitaxel resistance in P-glycoprotein overexpressing cancer cells" in European Journal of Pharmaceutical Sciences, 105 (2017):159-168,
https://doi.org/10.1016/j.ejps.2017.05.011 . .