CEPHARANTHINE INHIBITS 2-STAGE TUMOR PROMOTION BY 12-O-TETRADECANOYLPHORBOL 13-ACETATE AND MEZEREIN ON SKIN TUMOR-FORMATION IN MICE INITIATED WITH 7,12-DIMETHYLBENZ[ALPHA]ANTHRACENE

Cepharanthine, isolated from Stephania cepharantha, is one of the bisbenzylisoquinoline-type alkaloids. 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-mu-g/mouse) and mezerein (5-mu-g/mouse) were found to be inhibited by topical application of cepharanthine, with a ED50 of 1.2-mu-mol and 1.4-mu-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-1 day-1) slightly suppressed the two-stage promotion of skin tumors by twice-weekly applications of 2.5-mu-g TPA for 2 weeks (first stage) followed by twice-weekly applications of 2.5-mu-g mezerein for 23 weeks (second stage) in ICR mice following initiation by 50-mu-g 7,12-dimethylbenz[a]anthracene. Oral administration of cepharanthine inhibits the tumor promotion in two-stage carcinogenesis in mouse skin.