Anti-tumor-promoting effects of isoflavonoids on Epstein-Barr virus activation and two-stage mouse skin carcinogenesis

As a part of screening studies for anti-tumor promoters, fifteen isoflavonoids isolated from plants of the genus Millettia (Leguminosae) were evaluated by examining their possible inhibitory effects on Epstein-Barr virus early antigen (EBV-EA) activation induced by 12-O-tetradecanoylphorbol-13-acetate in Raji cells. All of the compounds tested in this study showed inhibitory activity against EBV, without showing any cytotoxicity. Auriculasin (11) and millepurone (13), which is an oxidized isoflavone analogue, both having one or more prenyl side-chains and a 3',4'-dihydroxyphenyl group in the molecule, showed more potent activity than any of the other compounds tested. Furthermore, millepurone (13) exhibited a marked inhibitory effect on mouse skin tumor promotion in an in vivo two-stage carcinogenesis test. The results of the present investigation indicate that some of these isoflavonoids might be valuable anti-tumor promoters. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.