Mechanisms for the prevention of gastrointestinal cancer: the role of prostaglandin E2.
Carcinoma of the colon or rectum represents one of the most common malignancies worldwide with a higher prevalence in industrialized regions. Epidemiologic studies of individuals taking non-steroidal anti-inflammatory drugs (NSAIDs) have shown a significant reduction in colorectal cancer (CRC) mortality compared to those individuals not receiving these agents. NSAIDs inhibit the enzymatic activity of both isoforms of cyclooxygenase (COX-1 and COX-2), while COX-2-selective inhibitors have shown some efficacy in reducing polyp formation. COX-2-derived bioactive lipids, including the primary prostaglandin (PG) generated in colorectal tumors, PGE(2), are known to stimulate cell migration, proliferation and tumor-associated neovascularization while inhibiting cell death. Here we briefly review the role of NSAIDs in preventing CRC, as well as the proposed mechanism by which a COX-2-derived PG, PGE(2), promotes colon cancer.
Backlund
Michael G
MG
Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
Mann
Jason R
JR
Dubois
Raymond N
RN
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D000970:Antineoplastic Agents; D016718:Arachidonic Acid / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000517:prevention & control*; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D015232:Dinoprostone / Q000502:physiology*; D006801:Humans; D006911:Hydroxyprostaglandin Dehydrogenases / Q000378:metabolism; D008565:Membrane Proteins; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000970:Antineoplastic Agents; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D008565:Membrane Proteins; D016718:Arachidonic Acid; D006911:Hydroxyprostaglandin Dehydrogenases; C035859:15-hydroxyprostaglandin dehydrogenase; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone