Tumor-promoting activity of staurosporine, a protein kinase inhibitor on mouse skin.
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 micrograms of 7,12-dimethylbenz(a)anthracene, followed by repeated applications of 50 micrograms 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 micrograms 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.
Yoshizawa
S
S
National Cancer Center Research Institute, Tokyo, Japan.
Fujiki
H
H
Suguri
H
H
Suganuma
M
M
Nakayasu
M
M
Matsushima
R
R
Sugimura
T
T
D000470:Alkaloids / Q000633:toxicity*; D000818:Animals; D002460:Cell Line; D002472:Cell Transformation, Viral; D004789:Enzyme Activation; D004790:Enzyme Induction; D005260:Female; D004854:Herpesvirus 4, Human / Q000187:drug effects / Q000235:genetics; D006640:Histidine Decarboxylase / Q000096:biosynthesis; D006801:Humans; D008235:Lyngbya Toxins / Q000494:pharmacology; D051379:Mice; D008815:Mice, Inbred Strains; D009955:Ornithine Decarboxylase / Q000096:biosynthesis; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D047428:Protein Kinase Inhibitors; D012867:Skin / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D012878:Skin Neoplasms / Q000139:chemically induced*; D019311:Staurosporine
D000470:Alkaloids; D008235:Lyngbya Toxins; D047428:Protein Kinase Inhibitors; C022176:teleocidins; D011493:Protein Kinase C; D009955:Ornithine Decarboxylase; D006640:Histidine Decarboxylase; D019311:Staurosporine