Changes in gene expression contribute to cancer prevention by COX inhibitors.
Non-steroidal anti-inflammatory drugs (NSAIDs) are used primarily for the treatment of inflammatory diseases. However, certain NSAIDs also have a chemopreventive effect on the development of human colorectal and other cancers. NSAIDs inhibit cyclooxygenase-1 (COX-1) and/or cyclooxygenase-2 (COX-2) activity and considerable evidence supports a role for prostaglandins in cancer development. However, the chemopreventive effect of NSAIDs on colorectal and other cancers appears also to be partially independent of COX activity. COX inhibitors also alter the expression of a number of genes that influence cancer development. One such gene is NAG-1 (NSAID-Activated Gene), a critical gene regulated by a number of COX inhibitors and chemopreventive chemicals. Therefore, this article will discuss the evidence supporting the conclusion that the chemo-preventive activity of COX inhibitors is mediated, in part, by altered gene expression with an emphasis on NAG-1 studies. This review may also provide new insights into how chemicals and environmental factors influence cancer development. In view of the cardiovascular and gastrointestinal toxic side effects of COX-2 inhibitors and non-selective COX inhibitors, respectively, the results presented here may provide the basis for the development of a new family of anti-tumorigenic compounds acting independent of COX inhibition.
Baek
Seung Joon
SJ
University of Tennessee, Department of Pathobiology, College of Veterinary Medicine Knoxville, TN 37996, USA.
Eling
Thomas E
TE
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use; D016588:Anticarcinogenic Agents / Q000627:therapeutic use*; D002471:Cell Transformation, Neoplastic / Q000187:drug effects / Q000378:metabolism; D016861:Cyclooxygenase Inhibitors / Q000627:therapeutic use*; D016207:Cytokines / Q000235:genetics / Q000502:physiology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D055436:Growth Differentiation Factor 15; D006801:Humans; D051379:Mice; D009369:Neoplasms / Q000378:metabolism / Q000517:prevention & control*; D011453:Prostaglandins / Q000502:physiology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D016588:Anticarcinogenic Agents; D016861:Cyclooxygenase Inhibitors; D016207:Cytokines; C526140:GDF15 protein, human; C526141:Gdf15 protein, mouse; D055436:Growth Differentiation Factor 15; D011453:Prostaglandins