Activity of the non-steroidal anti-inflammatory drug indomethacin against colorectal cancer.
A substantial body of evidence from rodent colon carcinogenesis models, in vitro experiments with human colorectal cancer cells and limited clinical observations in humans suggest that the non-steroidal anti-inflammatory drug indomethacin has anti-colorectal cancer activity. However, although many mechanisms of the anti-neoplastic activity of indomethacin have been suggested, e.g., cyclooxygenase inhibition and peroxisome proliferator-activated receptor gamma activation, the precise relevance of the majority of in vitro pharmacological observations to the in vivo anti-neoplastic activity of indomethacin remains unclear. Herein, we review the existing literature describing the chemopreventative and chemotherapeutic efficacy of indomethacin against colorectal cancer, and draw together the disparate literature describing potential mechanisms of action of indomethacin in human colorectal cancer cells in vitro. Although indomethacin itself has significant adverse effects, including serious upper gastrointestinal toxicity, the development of novel derivatives that may have an improved safety profile means that further investigation of the anti-colorectal cancer activity of indomethacin is warranted.
Hull
M A
MA
Molecular Medicine Unit, University of Leeds, Clinical Sciences Building, St. James's University Hospital, Leeds, LS9 7TF, UK. M.A.Hull@leeds.ac.uk
Gardner
S H
SH
Hawcroft
G
G
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology* / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000517:prevention & control*; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology* / Q000627:therapeutic use; D018160:Receptors, Cytoplasmic and Nuclear / Q000187:drug effects / Q000378:metabolism; D014157:Transcription Factors / Q000187:drug effects / Q000378:metabolism
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000970:Antineoplastic Agents; D016861:Cyclooxygenase Inhibitors; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; D007213:Indomethacin