Millepachine showed novel antitumor effects in cisplatin-resistant human ovarian cancer through inhibiting drug efflux function of ATP-binding cassette transporters.

Millepachine (MIL), a bioactive natural chalcone from Chinese herbal medicine Millettia pachycarpa Benth, exhibits strong antitumor effects against many human cancer cells both in vitro and in vivo. In this study, we found that MIL significantly inhibited the proliferation of cisplatin-resistant A2780CP cells via inducing obvious G2/M arrest and apoptosis and down-regulating the activity of topoisomerase II protein. We further found that the mechanism by which MIL showed good antitumor effects in cisplatin-resistant human ovarian cancer was associated with inhibiting the expression of ATP-binding cassette transporters in cisplatin-resistant A2780CP cells. Importantly, MIL did not only significantly inhibit the tumor growth in cisplatin-sensitive A2780S xenograft model, with an inhibitory rate of 73.21%, but also inhibited the tumor growth in the cisplatin-resistant A2780CP xenograft model, with an inhibitory rate of 65.68% (p < 0.001 vs. control; p < 0.001 vs. DDP). In addition, MIL did not induce acquired drug resistance in A2780S tumor-bearing mice with an inhibitory rate of 60.03%. The promising in vitro and in vivo performance indicated that MIL exhibited potential significance for drug research and development.