Chemopreventive activity of celecoxib, a specific cyclooxygenase-2 inhibitor, and indomethacin against ultraviolet light-induced skin carcinogenesis

Susan M. Fischer, Herng Hsang Lo, Gary B. Gordon, Karen Seibert, Gary Kelloff, Ronald A. Lubet, Claudio J. Conti

Research output: Contribution to journalArticle

359 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)231-240
Number of pages10
JournalMolecular Carcinogenesis
Volume25
Issue number4
DOIs
StatePublished - Aug 17 1999

Keywords

  • Cyclooxygenase
  • Skin carcinogenesis
  • Ultraviolet light

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