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

Mol Carcinog. 1999 Aug;25(4):231-40.


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 (4ppm) 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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology
  • Body Weight / drug effects
  • Celecoxib
  • Cell Division
  • Cyclooxygenase 2
  • Cyclooxygenase 2 Inhibitors
  • Cyclooxygenase Inhibitors / pharmacology*
  • Dinoprostone / biosynthesis
  • Dose-Response Relationship, Radiation
  • Feeding Behavior / drug effects
  • Indomethacin / pharmacology*
  • Isoenzymes / drug effects
  • Mice
  • Mice, Hairless
  • Neoplasms, Radiation-Induced / pathology
  • Neoplasms, Radiation-Induced / prevention & control*
  • Prostaglandin-Endoperoxide Synthases / drug effects
  • Pyrazoles
  • Skin Neoplasms / pathology
  • Skin Neoplasms / prevention & control*
  • Sulfonamides / pharmacology*
  • Ultraviolet Rays


  • Anti-Inflammatory Agents, Non-Steroidal
  • Cyclooxygenase 2 Inhibitors
  • Cyclooxygenase Inhibitors
  • Isoenzymes
  • Pyrazoles
  • Sulfonamides
  • Cyclooxygenase 2
  • Prostaglandin-Endoperoxide Synthases
  • Celecoxib
  • Dinoprostone
  • Indomethacin