Barbigerone reverses multidrug resistance in breast MCF-7/ADR cells.

: Development of agents to overcome multidrug resistance (MDR) is one of the important strategies in cancer chemotherapy, and P-glycoprotein (P-gp) correlates with the degree of resistance. As a naturally occurring isoflavone, whether barbigerone (BA) could reverse MDR, is unknown. In this paper, we evaluated effects of BA on reversing P-gp mediated MDR of adriamycin (ADR)-resistant human breast carcinoma (MCF-7/ADR) cells. BA (0.5 μM) treatment showed strong potency to increase ADR cytotoxicity toward MCF-7/ADR cells. It was also demonstrated that BA time- and dose-dependently increased accumulations of ADR and reduced the efflux in MCF-7/ADR cells, pretreatment of these cells with BA might relocalized ADR to the nuclei. Furthermore, the results also revealed that BA did not affect P-gp, but alter P-gp ATPase activity. Intravenous administration of BA significantly increased anticancer efficacy of ADR to MCF-7/ADR xenograft model in nude mice. These results revealed that BA might reverse P-gp mediated MDR through inhibition of ATPase activity, which indicated a novel use of BA as a potent candidate for cancer chemotherapy.