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Inhibitory Effects of Perillyl Alcohol on UVB-induced Murine Skin Cancer and AP-1 Transactivation¹

Department of Radiation Oncology, The University of Arizona Health Sciences Center, Tucson, Arizona 85724 [M. B., W. C., H. L. G., G. T. B.], and The Hormel Institute, University of Minnesota, Austin, Minnesota 55912 [C. H., Z. D.]

The monoterpene perillyl alcohol (POH) has proven efficacious against the formation and progression of a variety of cancers. In this study, we tested the ability of POH to inhibit photocarcinogenesis in a nonmelanoma model of mouse skin carcinogenesis and its ability to inhibit UVB-induced activator protein 1 (AP-1) transactivation in mouse skin and human keratinocytes. POH (10 mM) was applied topically to the ears and shaved dorsal surface of groups of 35 BALB/c mice throughout the experiment, during and after UVB treatment. Topical POH significantly inhibited tumor incidence and multiplicity, average tumor size, and the average tumor burden/mouse without any apparent toxicity. POH inhibited UVB-induced AP-1 transactivation in both cultured human keratinocytes and transgenic mice that stably express a luciferase reporter driven by AP-1 elements. The results suggest that POH might be used for chemoprevention of human skin cancer, and that inhibition of AP-1 activity is functionally related to inhibition of skin carcinogenesis.

¹ Supported by NIH Grant CA-27502.

² To whom requests for reprints should be addressed, at Department of Radiation Oncology, The University of Arizona Health Sciences Center, 1515 North Campbell Avenue, Tucson, AZ 85724. Phone: (520) 626-6006; Fax: (520) 626-4480.

Received 9/12/97. Accepted 12/16/97.

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