DTA0100, dual topoisomerase II and microtubule inhibitor, evades paclitaxel resistance in P-glycoprotein overexpressing cancer cells
Аутори
Podolski-Renić, AnaBanković, Jasna
Dinić, Jelena
Rios-Luci, Carla
Fernandes, Miguel X.
Ortega, Nuria
Kovačević Grujičić, Nataša
Martin, Victor S.
Padron, Jose M.
Pesić, Milica
Чланак у часопису (Рецензирана верзија)
Метаподаци
Приказ свих података о документуАпстракт
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 beta-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 an...d subsequent apoptosis. The fine-tuning in beta-tubulin isoforms expression observed in multi drug resistant cancer cells may influence the efficacy of DTA0100. Importantly, DTA0100 blocked the Pglycoprotein function in both multi-drug resistant cancer cell lines without inducing the increase in Pglycoprotein 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.
Кључне речи:
P-glycoprotein / Paclitaxel / Multi-drug resistance / Microtubule targeting agents / Colchicine / beta-tubulinИзвор:
European Journal of Pharmaceutical Sciences, 2017, 105, 159-168Издавач:
- Elsevier Science Bv, Amsterdam
Финансирање / пројекти:
- Идентификација молекуларних маркера за предикцију прогресије тумора, одговора на терапију и исхода болести (RS-MESTD-Integrated and Interdisciplinary Research (IIR or III)-41031)
- EU Research Potential [FP7-REGPOT-2012-CT2012-31637-IMBRAIN]
- European Regional Development Fund (FEDER)
- Spanish MINECO [CTQ2014-56362- C2-1- P]
Напомена:
- Related to published version: https://imagine.imgge.bg.ac.rs/handle/123456789/1079
- This is the peer reviewed version of the paper: Podolski-Renić, A., Banković, J., Dinić, J., Rios-Luci, C., Fernandes, M. X., Ortega, N., Kovačević Grujičić, N., Martin, V. S., Padron, J. M., & Pesić, M. (2017). DTA0100, dual topoisomerase II and microtubule inhibitor, evades paclitaxel resistance in P-glycoprotein overexpressing cancer cells. European Journal of Pharmaceutical Sciences, 105, 159–168. https://doi.org/10.1016/j.ejps.2017.05.011
Повезане информације:
- Друга верзија
https://imagine.imgge.bg.ac.rs/handle/123456789/1079
DOI: 10.1016/j.ejps.2017.05.011
ISSN: 0928-0987
PubMed: 28502672
WoS: 000404500900019
Scopus: 2-s2.0-85019439523
Институција/група
Institut za molekularnu genetiku i genetičko inženjerstvoTY - JOUR AU - Podolski-Renić, Ana AU - Banković, Jasna AU - Dinić, Jelena AU - Rios-Luci, Carla AU - Fernandes, Miguel X. AU - Ortega, Nuria AU - Kovačević Grujičić, Nataša AU - Martin, Victor S. AU - Padron, Jose M. AU - Pesić, Milica PY - 2017 UR - https://imagine.imgge.bg.ac.rs/handle/123456789/1766 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 beta-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 beta-tubulin isoforms expression observed in multi drug resistant cancer cells may influence the efficacy of DTA0100. Importantly, DTA0100 blocked the Pglycoprotein function in both multi-drug resistant cancer cell lines without inducing the increase in Pglycoprotein 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 - Elsevier Science Bv, Amsterdam T2 - European Journal of Pharmaceutical Sciences T1 - DTA0100, dual topoisomerase II and microtubule inhibitor, evades paclitaxel resistance in P-glycoprotein overexpressing cancer cells EP - 168 SP - 159 VL - 105 DO - 10.1016/j.ejps.2017.05.011 ER -
@article{ author = "Podolski-Renić, Ana and Banković, Jasna and Dinić, Jelena and Rios-Luci, Carla and Fernandes, Miguel X. and Ortega, Nuria and Kovačević Grujičić, Nataša and Martin, Victor S. and Padron, Jose M. and Pesić, 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 beta-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 beta-tubulin isoforms expression observed in multi drug resistant cancer cells may influence the efficacy of DTA0100. Importantly, DTA0100 blocked the Pglycoprotein function in both multi-drug resistant cancer cell lines without inducing the increase in Pglycoprotein 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 = "Elsevier Science Bv, Amsterdam", journal = "European Journal of Pharmaceutical Sciences", title = "DTA0100, dual topoisomerase II and microtubule inhibitor, evades paclitaxel resistance in P-glycoprotein overexpressing cancer cells", pages = "168-159", volume = "105", doi = "10.1016/j.ejps.2017.05.011" }
Podolski-Renić, A., Banković, J., Dinić, J., Rios-Luci, C., Fernandes, M. X., Ortega, N., Kovačević Grujičić, N., Martin, V. S., Padron, J. M.,& Pesić, M.. (2017). DTA0100, dual topoisomerase II and microtubule inhibitor, evades paclitaxel resistance in P-glycoprotein overexpressing cancer cells. in European Journal of Pharmaceutical Sciences Elsevier Science Bv, Amsterdam., 105, 159-168. https://doi.org/10.1016/j.ejps.2017.05.011
Podolski-Renić A, Banković J, Dinić J, Rios-Luci C, Fernandes MX, Ortega N, Kovačević Grujičić N, Martin VS, Padron JM, Pesić 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, Rios-Luci, Carla, Fernandes, Miguel X., Ortega, Nuria, Kovačević Grujičić, Nataša, Martin, Victor S., Padron, Jose M., Pesić, 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 . .