The role of arachidonic acid regulatory enzymes in colorectal disease.
OBJECTIVE
Nonsteroidal anti-inflammatory drugs have a wide ranging effect on diseases of the colon and rectum. Interestingly, nonsteroidal anti-inflammatory drugs seem to play a beneficial role in colorectal cancer chemoprevention and adenoma regression, but may have a deleterious effect in inflammatory bowel disease. Prostaglandin inhibition is central to both the beneficial and toxic effects of this class of drugs. Arachidonic acid metabolism is essential to prostaglandin synthesis.


METHODS
A Medline search using "nonsteroidal anti-inflammatory drugs," "colon cancer," "inflammatory bowel disease," "colitis," "COX inhibitors," "arachidonic acid," and "chemoprevention" as key words was performed for English-language articles. Further references were obtained through cross-referencing the bibliography cited in each work.


RESULTS
Based on numerous studies, nonsteroidal anti-inflammatory drugs have a beneficial role in colon cancer and colonic adenomas. However, they have been reported to have a deleterious effect on the colon in inflammatory bowel disease and have been shown to cause colitis. Nonsteroidal anti-inflammatory drugs work via multiple pathways, some well defined, and others unknown.


CONCLUSIONS
In the new millennium, nonsteroidal anti-inflammatory drugs may be used for chemoprevention of colorectal and other cancers. In addition, they may be used in combination with surgery and chemotherapy to primarily treat colorectal carcinoma. Undoubtedly, the use of novel cyclooxygenase inhibitors with less of a toxicity profile will allow more widespread use of nonsteroidal anti-inflammatory drugs for a variety of diseases. The future of this class of drugs is promising.
Abir
Farshad
F
Department of Surgery, Yale University School of Medicine, New Haven, Connecticut 06520-8062, USA.
Alva
Suraj
S
Kaminski
Donald L
DL
Longo
Walter E
WE
D000236:Adenoma / Q000517:prevention & control; D011125:Adenomatous Polyposis Coli / Q000517:prevention & control; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D016718:Arachidonic Acid / Q000378:metabolism*; D003108:Colonic Diseases / Q000517:prevention & control*; D015179:Colorectal Neoplasms / Q000517:prevention & control; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D004760:Enterocolitis / Q000469:parasitology; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000517:prevention & control; D011451:Prostaglandin-Endoperoxide Synthases / Q000502:physiology*; D012002:Rectal Diseases / Q000517:prevention & control*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D016861:Cyclooxygenase Inhibitors; D016718:Arachidonic Acid; D011451:Prostaglandin-Endoperoxide Synthases