Structure-activity relationship of flavonoids for inhibition of epidermal growth factor-induced transformation of JB6 Cl 41 cells.
2007
We found that quercetin, myricetin, quercetagetin, fisetin, (−)-epigallocatechin gallate (EGCG), and theaflavins, among 24 flavonoids examined, markedly inhibited epidermal growth factor (EGF)-induced cell transformation of mouse epidermal JB6 Cl 41 cells. The six flavonoids suppressed the EGF-induced activation of activator protein 1 (AP-1). In addition, myricetin, quercetagetin, EGCG, and theaflavins directly inhibited EGF-induced phosphatidylinositol 3-kinase (PI3K) activation. The important structural features of flavonoids for cell transformation-inhibitory activity are 3′- and 4′-OH on the B-ring, 3-OH on the C-ring, C2C3 double bond in the C-ring, and the phenylchromone (C6C5C6) skeleton in the flavonols, and the galloyl group in EGCG and theaflavins. Our results provide new insight into possible mechanisms of the anti-carcinogenic effects of flavonoids, and could help to provide a basis for the design of novel cancer chemopreventive agents. © 2007 Wiley-Liss, Inc.
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