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

National Cancer Center Research Institute [S. Y., H. F., H. S., M. S., M. N., R. M.], and National Cancer Center [T. S.], Chuo-ku, Tokyo 104, Japan

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 nM) and Epstein-Barr virus early antigen in Raji cells (50% effective dose = 3.4 nM) 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 µg of 7,12-dimethylbenz(a)anthracene, followed by repeated applications of 50 µg 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 µg of staurosporine resulted in 33% of tumor-bearing mice at Wk 30. In addition, staurosporine 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.

¹ This work was supported in part by Grants-in-Aid for Cancer Research from the Ministry of Education, Science, and Culture; a grant for the Program for a Comprehensive 10-Year Strategy for Cancer Control from the Ministry of Health and Welfare of Japan; and by grants from the Foundation for Promotion of Cancer Research, the Princess Takamatsu Cancer Research Foundation, and the Smoking Research Foundation.

² To whom requests for reprints should be addressed.

Received 7/ 6/89. Revised 3/26/90.

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