Cyclooxygenase Inhibition and Mechanisms of Colorectal Cancer Prevention

Colorectal cancer is a leading cause of cancer death throughout the world. The high prevalence and mortality associated with colon cancer make effective prevention and treatment an important public health and economic concern. Among the few agents known to inhibit colorectal tumorigenesis are the nonsteroidal anti-inflammatory drugs or NSAIDs, as well as newer agents such as celecoxib and rofecoxib. Both epidemiologic studies and investigations with animals show that these compounds possess marked anti-colorectal cancer properties. NSAIDS are widely known to be inhibitors of the cyclooxygenase (COX) enzymes, and it is thought that the chemopreventive effects of NSAIDs are at least in part due to this ability to inhibit COX. More recent studies, however, have suggested that NSAIDs may also exert anti-cancer effects through mechanisms independent of COX inhibition. COX-dependent and COX-independent mechanisms are not mutually exclusive and it is likely that both are involved in the biological activity of NSAIDs.