Recent research and accumulating evidence has shown that nonsteroidal anti-inflammatory drugs (NSAIDs) have a shot in the battle against cancer. Recent experiments show that NSAIDs stimulate cell apoptosis and inhibit angiogenesis. In fact, further studies have shown that long-term aspirin users have a significantly reduced risk of colorectal cancer than nonusers. However, despite these discoveries, the efficacy and safety of long-term NSAID administration as anticancer agents remains unproven.
NSAIDs have the ability to inhibit the COX activity of the enzyme prostaglandin G/H-synthase. This blocks the biosynthesis of prostaglandins. Prostaglandins have a wide range of physiological effects including the regulation of the contraction and relaxation of smooth muscle tissue. The prostaglandin synthesis pathway contains a rate-limiting step where cyclooxygenase (COX) catalyzes the conversion of arachidonic acid to an unstable prostaglandin endoperoxide intermediate. This intermediate is converted to a series of different prostaglandins, most of which are pro-inflammatory, that are specific to a particular cell type or tissue. COX has a role during the early stages of intestinal tumorigenesis and during the later stages of colorectal carinogenesis. NSAIDs serve as COX-inhibitors.
In the mid 1970s, a study reported that the concentration of prostaglandin E2 (one product from the PG intermediate) was higher in human colorectal tumor tissue than in surrounding normal mucosa. Further experimentation that showed NSAIDs inhibit chemically induced colorectal cancer in rats. NSAIDs typically reduce the number and size of tumors by 40-60%. However, the tumors were suppressed, not eliminated.
Mechanistic studies of NSAIDs have shown that apoptosis, programmed cell death, is restored in APC-deficient cells. Somatic mutations in the APC gene result in the partial suppression of apoptosis and lead to tumor growth. NSAIDs stimulate apoptosis in APC-deficient cells that have not become malignant. Apoptosis becomes more and more inhibited during the development of colorectal cancer. There is a strong correlation between apoptosis inhibition and the increasing expression of COX.
Experimentation suggest NSAIDs are promising anti-cancer drugs. There are many unanswered questions, but continued experimentation will sustain progress in this exciting area of science.