Novel D-ring Analog of Epigallocatechin-3-gallate Inhibits Tumor Growth and VEGF Expression in Breast Carcinoma Cells

• Published in: Anticancer research Vol. 25; no. 1A; pp. 397 - 402
• Main Authors: WALEH, Nahid S, CHAO, Wan-Ru, BENSARI, Ahlem, ZAVERI, Nurulain T
• Format: Journal Article
• Language: English
• Published: Attiki International Institute of Anticancer Research 01.01.2005
• Subjects: Biological and medical sciences; Breast Neoplasms - drug therapy; Breast Neoplasms - metabolism; Breast Neoplasms - pathology; Catechin - analogs & derivatives; Catechin - chemistry; Catechin - pharmacology; Cell Hypoxia; Cell Line, Tumor; Cell Proliferation - drug effects; Gynecology. Andrology. Obstetrics; Humans; Mammary gland diseases; Medical sciences; RNA, Messenger - biosynthesis; RNA, Messenger - genetics; Tumors; Vascular Endothelial Growth Factor A - antagonists & inhibitors; Vascular Endothelial Growth Factor A - biosynthesis; Vascular Endothelial Growth Factor A - genetics; Chemoprophylaxis; EGCG analog; VEGF; Malignant tumor; Prevention; Mammary gland diseases; Breast carcinoma; epigallocatechin-3-gallate; Chemotherapy; Cancerology; Vascular endothelium growth factor; Treatment; chemoprevention; Tumor growth; Analog; Ring; Inhibitor; Green tea
• ISSN: 0250-7005; 1791-7530

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.