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KMID : 1140120070120030163
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Cancer Prevention Research
2007 Volume.12 No. 3 p.163 ~ p.173
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Regulation of Cellular Signal Transduction by Flavonoids
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Lee Eung-Ryoung
Kang Geun-Ho
Kang Yong-Jin
Kim Woo-Yeul
Choi Hye-Yeon
Kim Bong-Woo
Jeong Hyo-Soon
Cho Ssang-Goo
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Abstract
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Many studies revealed the neuroprotective, cardioprotective, and chemopreventive actions of dietary flavonoids. The plausible mechanistic interpretation of the various effects of flavonoids was concentrated on the anti-oxidant or free radical-scavenging properties of these phytochemicals, both in model systems and under in vivo conditions. While there has been a major focus on the anti-oxidant properties, there is an emerging view that flavonoids and their in vivo metabolites, do not act as conventional hydrogen-donating anti-oxidants, but they may exert regulatory functions in cells through actions at protein kinase or lipid kinase signaling pathways. Flavonoids and more recently their metabolites, have been reported to act at phosphoinositide 3-kinase (PI 3-kinase), Akt/protein kinase B (Akt/PKB), protein kinase C (PKC), mitogen activated protein kinase (MAP kinase), and various tyrosine kinases signaling cascades. Inhibitory or stimulatory actions at these pathways are likely to affect cellular function profoundly by altering the phosphorylation state of target molecules and by modulating gene expression. A clear understanding of the mechanisms of action of flavonoids, either as anti-oxidants or modulators of cellular signaling pathways, and the influence of their metabolism on these properties are key to the evaluation of these potent biomolecules as anti-cancer agents, cardio-protectants, and inhibitors of neurodegeneration. (Cancer Prev Res 12, 163-173, 2007)
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KEYWORD
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Flavonoid, Anti-oxidant, MAP kinase, PI3-Kinase, Apoptosis, Flavonoid metabolite, Free radicals
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