Inhibitory effect of flavonoids from Citrus plants on Epstein–Barr virus activation and two-stage carcinogenesis of skin tumors

To search for possible anti-tumor promoters, thirteen flavones (1–13) obtained from the peel of Citrus plants were examined for their inhibitory effects on the Epstein–Barr virus early antigen (EBV-EA) activation by a short-term in vitro assay. Of these flavones, 3,5,6,7,8,3′,4′-heptamethoxyflavone (HPT) (13) exhibited significant inhibitory effects on the EBV-EA activation induced by the tumor promoter, 12-O-tetradecanoylphorbol 13-acetate (TPA). Further, compound 13 exhibited remarkable inhibitory effects on mouse skin tumor promotion in an in vivo two-stage carcinogenesis test.