Open Access
Article
Chemoprevention by resveratrol: molecular mechanisms and therapeutic potential
Sharmila Shankar1,Gyanendra Singh1,Rakesh K Srivastava1
1
Department of Biochemistry, University of Texas Health Science Center at Tyler, Tyler, Texas 75703, USA
DOI: 10.2741/2432 Volume 12 Issue 13, pp.4839-4854
Published: 01 September 2007
(This article belongs to the Special Issue Cancer chemoprevention - 2)
Abstract

Resveratrol, a polyphenol found in numerous plant species, including mulberries, peanuts and grapes, has shown to possess chemopreventive properties against several cancers, and cardiovascular diseases. Recently, resveratrol has been shown to have positive effects on age longevity, lipid levels and a preventative quality against certain cancers and viral infections. Resveratrol induces apoptosis by up-regulating the expression of Bax, Bak, PUMA, Noxa, Bim, p53, TRAIL, TRAIL-R1/DR4 and TRAIL-R2/DR5 and simultaneously down-regulating the expression of Bcl-2, Bcl-XL, Mcl-1 and survivin. Resveratrol causes growth arrest at G1 and G1/S phases of cell cycle by inducing the expression of CDK inhibitors p21/WAF1/CIP1 and p27/KIP1. Resveratrol has also been shown to reduce inflammation via inhibition of prostaglandin production, cyclooxygenase-2 activity, and nuclear factor-kappaB activity. Modulation of cell signaling pathway by resveratrol explains its diverse bioactivities related with human health. Resveratrol also potentiates the apoptotic effects of cytokines, chemotherapeutic agents and gamma-radiation. Pharmacokinetic and pharmacodynamic studies demonstrated that the main target organs of resveratrol are liver and kidney, and it is metabolized by hydroxylation, glucuronidation, sulfation and hydrogenation. As a chemoprevention agent, resveratrol has been shown to inhibit tumor initiation, promotion, and progression. There is growing evidence that resveratrol can prevent or delay the onset of various cancers, heart diseases, ischemic and chemically induced injuries, pathological inflammation and viral infections. This review summarizes the molecular mechanisms of resveratrol and its clinical benefits for human diseases.

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Sharmila Shankar, Gyanendra Singh, Rakesh K Srivastava. Chemoprevention by resveratrol: molecular mechanisms and therapeutic potential. Frontiers in Bioscience-Landmark. 2007. 12(13); 4839-4854.