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Molecular Mechanism for Various Pharmacological Activities of NSAIDS

NSAIDs: Old Drugs Reveal New Anticancer Targets

Southern Research Institute, 2000 9th Avenue South, Birmingham AL, 35205, USA
The University of Alabama at Birmingham, 703 19th Street South, Birmingham AL, 35294, USA
Vivo Biosciences Inc., 1601 12th Avenue South, Birmingham AL, 35205, USA
Author to whom correspondence should be addressed.
Pharmaceuticals 2010, 3(5), 1652-1667;
Received: 16 March 2010 / Revised: 5 May 2010 / Accepted: 10 May 2010 / Published: 25 May 2010
(This article belongs to the Special Issue Non-Steroidal Anti-Inflammatory Drugs)
There is compelling evidence that nonsteroidal anti-inflammatory drugs (NSAIDs) and cyclooxygenase-2 selective inhibitors have antineoplastic activity, but toxicity from cyclooxygenase (COX) inhibition and the suppression of physiologically important prostaglandins limits their use for cancer chemoprevention. Previous studies as reviewed here suggest that the mechanism for their anticancer properties does not require COX inhibition, but instead involves an off-target effect. In support of this possibility, recent molecular modeling studies have shown that the NSAID sulindac can be chemically modified to selectively design out its COX-1 and COX-2 inhibitory activity. Unexpectedly, certain derivatives that were synthesized based on in silico modeling displayed increased potency to inhibit tumor cell growth. Other experiments have shown that sulindac can inhibit phosphodiesterase to increase intracellular cyclic GMP levels and that this activity is closely associated with its ability to selectively induce apoptosis of tumor cells. Together, these studies suggest that COX-independent mechanisms can be targeted to develop safer and more efficacious drugs for cancer chemoprevention. View Full-Text
Keywords: NSAIDs; sulindac; cancer; colon; chemoprevention NSAIDs; sulindac; cancer; colon; chemoprevention
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MDPI and ACS Style

Piazza, G.A.; Keeton, A.B.; Tinsley, H.N.; Whitt, J.D.; Gary, B.D.; Mathew, B.; Singh, R.; Grizzle, W.E.; Reynolds, R.C. NSAIDs: Old Drugs Reveal New Anticancer Targets. Pharmaceuticals 2010, 3, 1652-1667.

AMA Style

Piazza GA, Keeton AB, Tinsley HN, Whitt JD, Gary BD, Mathew B, Singh R, Grizzle WE, Reynolds RC. NSAIDs: Old Drugs Reveal New Anticancer Targets. Pharmaceuticals. 2010; 3(5):1652-1667.

Chicago/Turabian Style

Piazza, Gary A., Adam B. Keeton, Heather N. Tinsley, Jason D. Whitt, Bernard D. Gary, Bini Mathew, Raj Singh, William E. Grizzle, and Robert C. Reynolds. 2010. "NSAIDs: Old Drugs Reveal New Anticancer Targets" Pharmaceuticals 3, no. 5: 1652-1667.

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