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KMID : 1140120050100020089
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Cancer Prevention Research
2005 Volume.10 No. 2 p.89 ~ p.98
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Molecular Mechanisms Underlying Chemoprevention with Resveratrol
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Kundu Joydeb Kumar
Surh Young-Joon
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Abstract
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Chemoprevention has been come up as a frontline strategy to fight against cancer. One of the strategies for chemoprevention include the inhibition of phase I xenobiotic metabolizing enzymes responsible for activating procarcinogens and the induction of phase II enzymes facilitating detoxification or antioxidantive defense. Since tumor promotion is a reversible process that involves inappropriate functioning of intracellular signal transduction pathways, controlling deregulated cell signaling network by dietary phytochemicals constitute a rational approach to achieve chemoprevention. Resveratrol, a major constituent of red wine, grapes and other edible plant species, has been documented as an effective chemopreventive agent. While depicting the molecular mechanisms underlying chemopreventive activity of resveratrol, it has been shown that resveratrol can block tumor initiation process by targeting cytochrome P450 enzymes that activate procarcinogens. Resveratrol also induces several phase II detoxification or antioxidant enzymes by activating a redox-sensitive transcription factor nuclear factor E2-related factor-2, thereby conferring protection against initiation of carcinogenesis. As inflammation is closely linked to tumor promotion, a variety of antiinflammatory phytochemicals exert anti-tumor promotional effects by down-regulating aberrantly expressed cyclooxygenase-2. Multiple lines of evidence suggest that resveratrol possesses anti-inflammatory and antiproliferative properties. Of the several intracellular signaling cascades that resveratrol targets, signaling via transcription factors NF-κB and/or AP-1 that regulates transcriptional activation of many proinflammatory and growth promoting genes appears to be the most important. This review will address the molecular basis of chemoprevention by resveratrol, particularly at the level of initiation and promotion stage of carcinogenesis.
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KEYWORD
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Chemoprevention, Resveratrol, Nrf2, NF-κB, AP-1, MAPKs
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