Cepharanthine inhibits two-stage tumor promotion by 12-O-tetradecanoylphorbol 13-acetate and mezerein on skin tumor formation in mice initiated with 7,12-dimethylbenz[a]anthracene

Summary Cepharanthine, isolated fromStephania cepharantha, is one of the bisbenzylisoquinoline-type alka-loids. We have found that it inhibits tumor promotion after topical application in two-stage carcinogenesis in mouse skin. Epidermal ornithine decarboxylase activities inhibited by topical application of cepharanthine, with an 5 g/mouse) and mezerein (5 g/mouse) were found to be inhibited by topical application of cepharanthine, with a ED₅₀ of 1.2 mol and 1.4 mol respectively. These inhibitory effects of cepharanthine are considered to be related to its antitumor activity in two-stage carcinogenesis in mouse skin. Cell-mediated immunosuppression by TPA was unaffected by topical application of cepharanthine. A diet containing 0.005% cepharanthine (about 0.5 mg mouse^– day^–) slightly suppressed the two-stage promotion of skin tumors by twice-weekly applications of 2.5 g TPA for 2 weeks (first stage) followed by twice-weekly applications of 2.5 g mezerein for 23 weeks (second stage) in ICR mice following initiation by 50 g 7,12-dimethylbenz[a]anthracene. Oral administration of cepharanthine inhibits the tumor promotion in two-stage carcinogenesis in mouse skin.Abbreviations DMBA 7,12-dimethylbenz[a]anthracene - DTH delayed-type hypersensitivity - ODC ornithine decarboxylase - TPA 12-O-tetradecanoylphorbol 13-acetate