Journal
BIOCHEMICAL SOCIETY TRANSACTIONS
Volume 33, Issue -, Pages 724-727Publisher
PORTLAND PRESS LTD
DOI: 10.1042/BST0330724
Keywords
apoptosis; carbonic anhydrase; cell cycle; coxib; cytochrome C; NAG-1 (non-steroidal anti-inflamniatory drug-activated gene)
Categories
Funding
- NCI NIH HHS [CA92423, CA35427] Funding Source: Medline
Ask authors/readers for more resources
INSAIDs (non-steroidal anti-inflammatory drugs) prevent colon and other cancers. The fact that NSAIDs inhibit the eicosanoid pathway prompted mechanistic drug-developmental work focusing on COX (cyclooxygenase) and its products. The increased prostaglandin E-2 levels and the overexpression of COX-2 in colon and many other cancers provided the rationale for clinical trials with COX-2 inhibitors for cancer prevention or treatment. However, one COX-2 inhibitor has been withdrawn from the market because of cardiovascular side effects, and there are concerns about a class effect. Evidence suggests that COX-2 may not be the only, or the ideal, target for cancer prevention; for example, COX-2 is not expressed in human aberrant crypt foci, the earliest recognizable pre-malignant lesion in the colon; COX-2 is expressed in less than half of the adenomas; in vitro data show that MAIDS do not require the presence of COX-2 to prevent cancer; in familial adenomatous polyposis, the COX-2 inhibitor, celecoxib, had a modest effect, which was weaker than that of a traditional NSAID; and COX-2-specific inhibitors have several COX-2-independent activities, which may account for part of their cancer-preventive properties. The multiple COX-2-indpendent targets, and the limitations of COX-2 inhibitors, suggest the need to explore targets other than COX-2.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available