The synthetic compound 2′-hydroxy-2,4,6′-trimethoxychalcone overcomes P-glycoprotein-mediated multi-drug resistance in drug-resistant uterine sarcoma MES-SA/DX5 cells

Abstract

The antitumor activity of a novel synthetic chalcone derivative, 2′-hydroxy-2,4,6′-trimethoxychalcone (1H3MC), was evaluated using the multi-drug-resistant human uterine sarcoma MES-SA/Dx5 cells. Treatment with 1H3MC reduced P-glycoprotein expression in a time-dependent manner and inhibited MES-SA/Dx5 cell proliferation. Cisplatin alone had no effect on cell viability, but combined treatment with cisplatin and 1H3MC exhibited synergistic cytotoxicity. Furthermore, the combination of cisplatin and 1H3MC synergistically cleaved both caspase-3 and its substrate protein, poly(ADP-ribose) polymerase, which resulted in the fragmentation of genomic DNA, a hallmark of apoptosis. These results suggest that 1H3MC is a promising adjuvant agent for overcoming P-glycoprotein-mediated multi-drug resistance in cancer cells.