DTA0100, dual topoisomerase II and microtubule inhibitor, evades paclitaxel resistance in P-glycoprotein overexpressing cancer cells
2017
Preuzimanje 🢃
Autori:
Podolski-Renić, AnaBanković, Jasna
Dinić, Jelena
Ríos-Luci, Carla
Fernandes, Miguel X.
Ortega, Nuria
Kovačević-Grujičić, Nataša
Martín, Víctor S.
Padrón, José M.
Pešić, Milica
Tip dokumenta:
Članak u časopisu (Recenzirana verzija)
Metapodaci
Prikaz svih podataka o dokumentuApstrakt:
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.
Napomena:
This is the peer reviewed version of the following article: 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. Eur. J. Pharm. Sci. 2017;105:159-168. http://dx.doi.org/10.1016/j.ejps.2017.05.011
Related to: https://radar.ibiss.bg.ac.rs/handle/123456789/2762
Ključne reči:
β-tubulin; Colchicine; Microtubule targeting agents; Multi-drug resistance; Paclitaxel; P-glycoproteinIzvor:
European Journal of Pharmaceutical Sciences, 2017, 105, 159-168Finansiranje / projekti:
- Identifikacija molekularnih markera za predikciju progresije tumora, odgovora na terapiju i ishoda bolesti (RS-MESTD-Integrated and Interdisciplinary Research (IIR or III)-41031)
- EU Research Potential (FP7-REGPOT- 2012-CT2012-31637-IMBRAIN)
- European Regional Development Fund (FEDER) and the Spanish MINECO (CTQ2014-56362- C2-1- P)
- COST Action CM1106 (Chemical Approaches to Targeting Drug Resistance in Cancer Stem Cells)
DOI: 10.1016/j.ejps.2017.05.011
ISSN: 0928-0987
PubMed: 28502672
WoS: 000404500900019
Scopus: 2-s2.0-85019439523
URI
https://www.sciencedirect.com/science/article/abs/pii/S0928098717302397https://radar.ibiss.bg.ac.rs/123456789/3873