Tumor-promoting Activity of Staurosporine, a Protein Kinase Inhibitor on Mouse Skin1

Staurosporine, which is a potent inhibitor of protein kinases, such as protein kinase C, inhibited both inductions of adhesion of human promyelocytic leukemia cells (50% effective dose = 9.0 n.\t) and EpsteinBarr virus early antigen in Raji cells (50% effective dose = 3.4 nivi) by teleocidin. However, Staurosporine induced irritation on mouse ear and histidine decarboxylase activity in mouse skin. It did not induce ornithine decarboxylase activity in mouse epidermis. The two-stage carcinogenesis experiments of Staurosporine were carried out at two different doses. Experiment 1 revealed that the group treatment with a single application of 100 fig of 7,12-dimethylbenz(fl)anthracene, followed by repeated ap plications of 50 ng of Staurosporine, resulted in 85.7% of tumor-bearing mice at Wk 30, whereas group treatment with Staurosporine alone or 7,12-dimethylbenz(a)anthracene alone gave 6.7% and 0%, respectively. Experiment 2 showed that group treatment with 7,12-dimethylbenz(a)anthracene followed by applications of 10 UKof Staurosporine resulted in 33% of tumor-bearing mice at Wk 30. In addition, Stauro sporine treatment reduced the percentages of tumor-bearing mice treated with teleocidin from 100% to 67% in Wk 15. These results demonstrated that Staurosporine is a weak tumor promoter of mouse skin compared with teleocidin, but Staurosporine has some potency to inhibit tumor promotion by teleocidin.