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.
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 micrograms/mouse) and mezerein (5 micrograms/mouse) were found to be inhibited by topical application of cepharanthine, with a ED50 of 1.2 mumol and 1.4 mumol 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 micrograms TPA for 2 weeks (first stage) followed by twice-weekly applications of 2.5 micrograms mezerein for 23 weeks (second stage) in ICR mice following initiation by 50 micrograms 7,12-dimethylbenz[a]anthracene. Oral administration of cepharanthine inhibits the tumor promotion in two-stage carcinogenesis in mouse skin.
Yasukawa
K
K
College of Pharmacy, Nihon University, Chiba, Japan.
Takido
M
M
Takeuchi
M
M
Akasu
M
M
Nakagawa
S
S
D015127:9,10-Dimethyl-1,2-benzanthracene / Q000494:pharmacology*; D000284:Administration, Oral; D000287:Administration, Topical; D000470:Alkaloids / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D044182:Benzylisoquinolines; D002273:Carcinogens / Q000494:pharmacology*; D004224:Diterpenes; D004347:Drug Interactions; D004790:Enzyme Induction / Q000187:drug effects; D005260:Female; D007111:Immunity, Cellular / Q000187:drug effects; D051379:Mice; D008813:Mice, Inbred ICR; D009955:Ornithine Decarboxylase / Q000096:biosynthesis; D012867:Skin / Q000187:drug effects / Q000201:enzymology; D012878:Skin Neoplasms / Q000139:chemically induced* / Q000201:enzymology / Q000276:immunology; D013729:Terpenes / Q000494:pharmacology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D052117:Benzodioxoles
D015127:9,10-Dimethyl-1,2-benzanthracene; D000470:Alkaloids; D044182:Benzylisoquinolines; D002273:Carcinogens; D004224:Diterpenes; D009955:Ornithine Decarboxylase; D013729:Terpenes; D013755:Tetradecanoylphorbol Acetate; C011309:mezerein; C006947:cepharanthine; D052117:Benzodioxoles