Inhibition of tumor formation from grafted murine papilloma cells by treatment of grafts with staurosporine, an inducer of squamous differentiation.
The microbial alkaloid staurosporine induces responses associated with protein kinase C activation, resulting in terminal differentiation in cultures of both normal and neoplastic mouse epidermal cells. As a cancer chemotherapy model, we treated grafts of mouse epidermal tumor cell lines 308 and SP-1 repeatedly with staurosporine. A dose-dependent inhibition of tumor formation, maximal at 0.025 nmol per treatment, was observed. Higher and lower doses were less effective, suggesting a specific target for staurosporine action. A single, low-dose treatment 2 weeks after grafting also markedly reduced tumor formation. Although in vitro evidence suggests that staurosporine-induced terminal squamous differentiation results from activation of protein kinase C, we found no inhibition of tumor growth in similar studies with the protein kinase C activator 12-O-tetradecanoylphorbol-13-acetate. These results indicate that staurosporine is an effective antitumor agent for eradicating squamous cell tumors in vivo.
Strickland
J E
JE
Laboratory of Cellular Carcinogenesis and Tumor Promotion, National Cancer Institute, Bethesda, MD 20892.
Dlugosz
A A
AA
Hennings
H
H
Yuspa
S H
SH
D000470:Alkaloids / Q000494:pharmacology*; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000473:pathology*; D002454:Cell Differentiation / Q000187:drug effects; D004195:Disease Models, Animal; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D010212:Papilloma / Q000188:drug therapy* / Q000473:pathology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000473:pathology; D019311:Staurosporine; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013997:Time Factors; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000470:Alkaloids; D000970:Antineoplastic Agents; D011493:Protein Kinase C; D019311:Staurosporine; D013755:Tetradecanoylphorbol Acetate