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© 1993 Oxford University Press

research-article

Inhibition of tumor formation from grafted murine papilloma cells by treatment of grafts with staurosporine, an inducer of squamous differentiation

James E. Strickland, Andrzej A. Dlugosz, Henry Hennings and Stuart H. Yuspa

Laboratory of Cellular Carcinogenesis and Tumor Promotion, National Cancer Institute Bethesda, MD 20892, USA

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.


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