Stimulatory Effect of Topical Application of Caffeine on UVB-Induced Apoptosis in Mouse Skin

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In an earlier study, we showed that oral administration of green tea or caffeine to SKH-1 mice for 2 weeks prior to a single application of UVB enhanced UVB-induced increases in the number of p53-positive cells, p21(WAF1/CIP1)-positive cells, and apoptotic sunburn cells in the epidermis. In the present study, we found that topical application of caffeine, a major chemopreventive agent in tea, to the dorsal skin of SKH-1 mice immediately after irradiation with UVB (30 mJ/cm2) enhanced UVB-induced apoptosis as measured by the number of morphologically distinct epidermal apoptotic sunburn cells and the number of caspase 3-positive cells. Time course studies indicated that UVB-induced increases in apoptotic sunburn cells were correlated with elevated levels of caspase 3, a key protease that becomes activated during an early stage of apoptosis. Topical application of caffeine immediately after UVB enhanced UVB-induced increases in caspase 3 (active form)-immunoreactive-positive cells and in caspase 3 enzyme activity in the epidermis. Topical application of caffeine had only a small stimulatory effect on UVB-induced increases in the level of wild-type p53 protein and these changes were not related temporally to caffeine-induced increases in apoptotic cells. There was little or no effect of topical applications of caffeine on epidermal cell proliferation as determined by bromodeoxyuridine (BrdU) incorporation into DNA. Topical application of (-)-epigallocatechin gallate (EGCG) to the dorsal skin of mice immediately after irradiation with UVB had a small inhibitory effect on UVB-induced increases in BrdU-positive cells in the basal layer of the epidermis, but this treatment had no effect on UVB-induced increases in apoptotic sunburn cells. The results of this study indicate a proapoptotic effect of topical application of caffeine on UVB-irradiated mouse skin.

Keywords: Apoptotic sunburn ce; Key words: UV carcinogenesis

Document Type: Research Article


Affiliations: 1: *Susan Lehman Cullman Laboratory for Cancer Research, Department of Chemical Biology, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ 08854-8020 2: ‡The Cancer Institute of New Jersey, New Brunswick, NJ 08901 3: §William M. and Myrle W. Garbe Professor of Cancer and Leukemia Research

Publication date: January 1, 2002

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  • Formerly: Oncology Research Incorporating Anti-Cancer Drug Design
    Oncology Research Featuring Preclinical and Clincal Cancer Therapeutics publishes research of the highest quality that contributes to an understanding of cancer in areas of molecular biology, cell biology, biochemistry, biophysics, genetics, biology, endocrinology, and immunology, as well as studies on the mechanism of action of carcinogens and therapeutic agents, reports dealing with cancer prevention and epidemiology, and clinical trials delineating effective new therapeutic regimens.
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