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  • Title: Novel D-ring analog of epigallocatechin-3-gallate inhibits tumor growth and VEGF expression in breast carcinoma cells.
    Author: Waleh NS, Chao WR, Bensari A, Zaveri NT.
    Journal: Anticancer Res; 2005; 25(1A):397-402. PubMed ID: 15816564.
    Abstract:
    The cancer chemopreventive activity of green tea and its major polyphenolic constituent, epigallocatechin-3-gallate (EGCG) have been attributed to its antioxidant, antiproliferative and antiangiogenic effects. Several new molecular targets for EGCG's anticarcinogenic activity have been proposed in the recent literature. However, the understanding of the molecular mechanisms of EGCG's activity in vivo have been confounded by its low oral bioavailability and low plasma levels. Studies of EGCG would be greatly aided by the availability of synthetic analogs of EGCG designed to understand the contributions of the A, B, and D-rings and the phenolic hydroxyl groups of EGCG to its molecular mechanisms of action. We recently reported the de novo synthesis of a D-ring analog of EGCG, with the objective of using such analogs to understand the molecular mechanisms of EGCG action. We report here the first studies with a synthetic D-ring analog of EGCG. We examined the ability of the synthetic D-ring analog to inhibit tumor cell proliferation in breast carcinoma cells. We also investigated the effect of the analog on stress-induced VEGF production in breast carcinoma cells using Northern analysis and quantitative RT-PCR. We report here that the synthetic D-ring analog inhibits breast cancer cell growth in vitro with potencies equivalent to those of EGCG. Our results also show that, like EGCG, the synthetic analog inhibits hypoxia- and serum starvation-induced production of VEGF mRNA in breast cancer cells. Such synthetic analogs are valuable for understanding the structure-function relationship of EGCG and identifying relevant mechanisms of the chemopreventive action of EGCG.
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