Mechanisms of inhibition of tumor angiogenesis and vascular tumor growth by epigallocatechin-3-gallate

Clin Cancer Res. 2004 Jul 15;10(14):4865-73. doi: 10.1158/1078-0432.CCR-03-0672.

Abstract

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Capillaries / drug effects
  • Capillaries / physiopathology
  • Catechin / analogs & derivatives*
  • Catechin / pharmacology*
  • Cell Line
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Dose-Response Relationship, Drug
  • Endothelial Cells / cytology
  • Endothelial Cells / drug effects
  • Endothelial Cells / metabolism
  • Humans
  • Male
  • Matrix Metalloproteinase 2 / metabolism
  • Matrix Metalloproteinase 9 / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Nude
  • NIH 3T3 Cells
  • Neovascularization, Pathologic / prevention & control*
  • Plant Preparations / pharmacology
  • Sarcoma, Kaposi / pathology
  • Sarcoma, Kaposi / prevention & control
  • Tea
  • Vascular Neoplasms / pathology
  • Vascular Neoplasms / prevention & control*
  • Xenograft Model Antitumor Assays

Substances

  • Plant Preparations
  • Tea
  • Catechin
  • epigallocatechin gallate
  • Matrix Metalloproteinase 2
  • Matrix Metalloproteinase 9