Bisbenzylisoquinoline Alkaloids Inhibit Tumor Promotion by 12-O-Tetradecanoylphorbol-13-Acetate in Two-Stage Carcinogenesis in Mouse Skin

Bisbenzylisoquinoline alkaloids, cepharanthine, berbamine and isotetrandrine, were isolated from Stephania cepharantha Hayata. These compounds inhibit arachidonic acid-induced inflammation in mice. We have found that cepharanthine inhibits tumor promotion after topical application and oral administration in two-stage carcinogenesis in mouse skin. Furthermore, topical application of berbamine (2 mumol/mouse) and isotetrandrine (2 mumol/mouse) markedly suppressed the tumor-promoting effect of 12-O-tetradecanoylphorbol-13-acetate (1 microgram) in mouse skin initiated with 7,12-dimethylbenz[a]anthracene (50 micrograms), at a grade corresponding to that of cepharanthine.