CHEMOPREVENTIVE EFFECTS OF NSAIDS AGAINST COLORECTAL-CANCER - REGULATION OF APOPTOSIS AND MITOSIS BY COX-1 AND COX-2

There is a wealth of evidence that nonsteroidal anti-inflammatory drug s (NSAIDs) can prevent colorectal cancer. In this article the role of cyclooxygenase 1 and 2, the principle target of NSAIDs, in the develop ment of colorectal cancer is reviewed. Cyclooxygenase is constituiteve ly expressed in normal colonic epithelium and surrounding stroma and c ould catalyse the generation of malondialdehyde which is a known mutag en and could initiate colorectal carcinogenesis; Mutation of APC which is an early genetic event leads to the expression of cyclooxygenase 2 which may prevents the appropriate apoptosis of mutant adenoma cells. Other proneoplastic effects of cyclooxygenase include changing the ac tion of Transforming Growth Factor beta from anti-proliferative to pro -proliferative, reducing adherence to extracellular matrix, promotes m etastasis and angiogenesis. These properties of cyclooxygenases sugges t that inhibition of both isoforms may have important protective effec ts against colorectal cancer.