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.