Nonsteroidal antiinflammatory drugs (
NSAIDs) induce apoptosis in a variety of
cancer cells, including those of colon, prostate, breast and
leukemia. In addition, the classical
NSAIDs sulindac and
aspirin are promising chemopreventive agents against
colon cancer.
NSAIDs inhibit
cyclooxygenases (COX) preventing the formation of
prostaglandins,
prostacyclin and
thromboxane.
NSAIDs also exert other
biological effects, including generation of
reactive oxygen species (ROS) and inhibition of
NF-kappaB-mediated signals. Despite many suggested mechanisms for their anticancer effects, it remains uncertain how they induce cell cycle arrest and apoptosis in
cancer cells. Furthermore, there is little information on the selectivity of
NSAIDs-mediated anticancer effects, although this is one of the most important issues in
cancer therapy. Increased understanding of the
biological basis for the anticancer activity of
NSAIDs and their selectivity is essential for future therapeutic advances. In this paper, we propose that increased ROS generation is one of the key mechanisms for
NSAIDs-mediated anticancer effects on various
cancer cells.