Inhibition of phorbol ester-caused induction of ornithine decarboxylase and tumor promotion in mouse skin by staurosporine, a potent inhibitor of protein kinase C.
We found that staurosporine, a potent inhibitor of protein kinase C, inhibits induction of ornithine decarboxylase (ODC) and tumor promotion caused by 12-O-tetradecanoylphorbol-13-acetate (TPA) in CD-1 mouse skin. When applied 5 min either before or after treatment with TPA, 1 microgram of staurosporine cause about 56% inhibition of ODC-induction by 5 micrograms of TPA. However, staurosporine did not inhibit TPA-induced epidermal hyperplasia. In two-stage carcinogenesis, staurosporine at 1 microgram was applied 5 min before application of 5 micrograms of TPA to the initiated skin: number of tumors was suppressed by about 40% although the incidence was not affected. No tumors developed when staurosporine alone was applied to the initiated skin.
Yamada
S
S
Department of Cancer Cell Research, University of Tokyo, Japan.
Hirota
K
K
Chida
K
K
Kuroki
T
T
D000470:Alkaloids / Q000494:pharmacology*; D000818:Animals; D003043:Cocarcinogenesis; D004790:Enzyme Induction / Q000187:drug effects; D006965:Hyperplasia; D051379:Mice; D009955:Ornithine Decarboxylase / Q000096:biosynthesis*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors*; D012878:Skin Neoplasms / Q000139:chemically induced*; D019311:Staurosporine; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*
D000470:Alkaloids; D011493:Protein Kinase C; D009955:Ornithine Decarboxylase; D019311:Staurosporine; D013755:Tetradecanoylphorbol Acetate