Berry anthocyanidins synergistically suppress growth and invasive potential of human non-small-cell lung cancer cells |
| |
Authors: | Kausar Hina Jeyabalan Jeyaprakash Aqil Farrukh Chabba Deepika Sidana Jasmeen Singh Inder P Gupta Ramesh C |
| |
Affiliation: | State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China |
| |
Abstract: | P-glycoprotein-mediated multidrug resistance (MDR) is a major limiting factor in the efficacy of most microtubule-targeting agents. Here, we investigated the novel, synthetic, and small-molecule microtubule-destabilizing agent, 2-(2-amino-5-(1-ethyl-1H-indol-5-yl) pyrimidin-4-yl) phenol (YHHU0895), for its anti-tumor activity and potential for overcoming P-glycoprotein-mediated MDR. YHHU0895 inhibited purified tubulin polymerization through binding to tubulin at the colchicine-binding site and significantly inhibited human tumor cell proliferation. Notably, P-glycoprotein-overexpressing KBV200 and K562/ADR cells, which are strongly resistant to colchicine, vinorelbine and paclitaxel, were sensitive to YHHU0895 both in vitro and in vivo. These findings indicate that YHHU0895 is a novel type of microtubule-destabilizing agent that has the potential for the treatment of patients with drug resistance mediated by P-glycoprotein. |
| |
Keywords: | YHHU0895 Microtubule P-glycoprotein Multidrug resistance Microtubule-destabilizing agent |
本文献已被 ScienceDirect PubMed 等数据库收录! |
|