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Clinical Cancer Research Vol. 10, 4865-4873, July 15, 2004
© 2004 American Association for Cancer Research


Experimental Therapeutics, Preclinical Pharmacology

Mechanisms of Inhibition of Tumor Angiogenesis and Vascular Tumor Growth by Epigallocatechin-3-Gallate

Gianfranco Fassina1,3, Roberta Venè2, Monica Morini1, Simona Minghelli4, Roberto Benelli2, Douglas M. Noonan1 and Adriana Albini2

1 Tumor Progression Unit and 2 Molecular Oncology Lab, Istituto Nazionale per la Ricerca sul Cancro, Genoa; 3 Istituto di Bioimmagini e Fisiologia Molecolare, Consiglio Nazionale delle Ricerche, section of Genoa; and 4 Advanced Biotechnology Center, Genoa, Italy

Purpose: Green tea consumption has been linked to a reduced occurrence of some tumor types. Current data indicate that the principal mediator of this chemopreventive effect is epigallocatechin-3-gallate (EGCG), the most abundant polyphenol found in dried tea leaves. Here, we examined the effects of this compound on the two key cell populations typically involved in tumor growth: tumor cells and endothelial cells.

Experimental Design: The effects of green tea and EGCG were tested in a highly vascular Kaposi’s sarcoma (KS) tumor model and on endothelial cells in a panel of in vivo and in vitro assays.

Results: EGCG inhibited KS-IMM cell growth and endothelial cell growth, chemotaxis, and invasion over a range of doses; high concentrations also induced tumor cell apoptosis. EGCG inhibited the metalloprotease-mediated gelatinolytic activity produced by endothelial cell supernatants and the formation of new capillary-like structures in vitro. Green tea or purified EGCG when administered to mice in the drinking water inhibited angiogenesis in vivo in the Matrigel sponge model and restrained KS tumor growth. Histological analysis of the tumors were consistent with an anti-angiogenic activity of EGCG and green tea.

Conclusions: These data suggest that the green tea gallate or its derivatives may find use in the prevention and treatment of vascular tumors in a chemoprevention or adjuvant setting.




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