Methoxy- and Fluoro-chalcone Derivatives Arrest Cell Cycle Progression and Induce Apoptosis in Human Melanoma Cell A375

Abstract

Because of the lack of efficacious treatments for advanced melanoma, new approaches are necessary. Chalcones are contained in fruits and vegetables, and have been suggested to be cancer-preventive. In this study, effects of synthetic chalcone derivatives were investigated especially on the proliferation of human melanoma cells and peripheral blood mononuclear cells (PBMCs). Four out of the 12 synthetic chalcones: 4-trifluoromethyl-4'-methoxychalcone (CH-1), 4-trifluoromethyl-2'-methoxychalcone (CH-3), 3-trifluoromethyl-2',4'-dimethoxychalcone (CH-4) and 3-trifluoromethyl-4'-methoxychalcone (CH-7) exhibited significant antiproliferative efficacies against the cultured cells of the human melanoma cell line A375. CH-1, CH-3, CH-4, and CH-7 induced cell cycle arrest at the S-G(2)/M phase within 24 h after the treatment. CH-3, CH-4, and CH-7 significantly activated caspase-3 at 12 h, subsequently induced apoptosis at 72 h. All chalcones inhibited concanavalin A-induced proliferation of PBMCs dose-dependently. Our results suggest that some methoxy- and/or fluoro-chalcones have antitumor efficacy by inducing apoptosis and the cell-cycle arrest.