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Chemopreventive activity of celecoxib, a specific cyclooxygenase‐2 inhibitor, and indomethacin against ultraviolet light–induced skin carcinogenesis
Author(s) -
Fischer Susan M.,
Lo HerngHsang,
Gordon Gary B.,
Seibert Karen,
Kelloff Gary,
Lubet Ronald A.,
Conti Claudio J.
Publication year - 1999
Publication title -
molecular carcinogenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.254
H-Index - 97
eISSN - 1098-2744
pISSN - 0899-1987
DOI - 10.1002/(sici)1098-2744(199908)25:4<231::aid-mc1>3.0.co;2-f
Subject(s) - celecoxib , biology , cyclooxygenase , carcinogenesis , pharmacology , ultraviolet light , ultraviolet , enzyme , biochemistry , materials science , chemistry , photochemistry , optoelectronics , gene
Epidemiological and dietary studies suggest that nonsteroidal anti‐inflammatory drugs (NSAIDs) reduce the risk of colon cancer, possibly through a mechanism involving inhibition of cyclooxygenase (COX)‐2, which is overexpressed in premalignant adenomatous polyps and colon cancer. Because ultraviolet light (UV) can induce COX‐2 and nonspecific NSAIDs can decrease UV‐induced skin cancer, we evaluated the ability of two compounds, celecoxib (a specific COX‐2 inhibitor) and indomethacin (a nonspecific NSAID), to block UV‐induced skin tumor development in SKH:HR‐1‐hrBr hairless mice. Mice fed 150 or 500 ppm celecoxib showed a dose‐dependent reduction (60% and 89%, respectively) in tumor yield. Indomethacin (4 ppm) reduced tumor yield by 78%. Although both acute and chronic UV exposure increased cell proliferation and edema, neither compound reduced these parameters. In contrast, UV‐induced prostaglandin synthesis in the epidermis was effectively blocked by both compounds. UV‐induced increases in COX‐2 expression in skin were also not altered in any of the treatment groups. Similarly, tumors that constitutively express high levels of COX‐2 displayed no reduction by treatment with celecoxib or indomethacin. The dramatic protective effects of celecoxib suggests that specific COX‐2 inhibitors may offer a way to safely reduce the risk of skin cancer in humans. Mol. Carcinog. 25:231–240, 1999. © 1999 Wiley‐Liss, Inc.