title: 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.
authors.affiliation: Department of Clinical Pharmacology, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, Tokyo, Japan. y984164@educs.ps.toyaku.ac.jp
authors.forename: Kayo
authors.initials: K
authors.lastname: Henmi
authors.forename: Yoko
authors.initials: Y
authors.lastname: Hiwatashi
authors.forename: Eri
authors.initials: E
authors.lastname: Hikita
authors.forename: Naoya
authors.initials: N
authors.lastname: Toyama
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Hirano
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D047188:Chalcones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D006801:Humans; D020287:In Situ Nick-End Labeling; D020128:Inhibitory Concentration 50; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000187:drug effects; D008545:Melanoma / Q000188:drug therapy / Q000473:pathology*; D015394:Molecular Structure; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D047188:Chalcones; D053148:Caspase 3