Barbigerone reverses multidrug resistance in breast MCF‐7/ADR cells |
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| Authors: | Fang Wang Heying Pei Li Zheng Wenshuang Wu Haoyu Ye Yanping Wang Lijuan Chen |
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| Affiliation: | 1. Department of pharmacy, East Branch of Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, Chengdu, Sichuan, China;2. State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu, Sichuan, China |
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| Abstract: | 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. |
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| Keywords: | barbigerone (BA) MCF‐7/ADR multidrug resistance (MDR) P‐glycoprotein (P‐gp) |
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