Green tea catechins inhibit angiogenesis through suppression of STAT3 activation

Breast Cancer Res Treat. 2009 Oct;117(3):505-15. doi: 10.1007/s10549-008-0196-x. Epub 2008 Sep 28.

Abstract

Previous studies indicate that green tea extract may inhibit breast cancer progression by blocking angiogenesis, although the molecular mechanisms are not well defined. We demonstrate that administration of Polyphenon E (Poly E), a standardized green tea extract, inhibited MDA-MB231 breast cancer and human dermal microvascular endothelial (HMVEC) cell migration and the expression of vascular endothelial growth factor (VEGF) and matrix metalloproteinase 9 (MMP9). In addition, Poly E inhibited VEGF-induced neovascularization in vivo. We also demonstrate that Poly E blocked signal transducers and activators of transcription (STAT) signaling by suppressing interferon-gamma (IFN-gamma)-induced gene transcription via IFN-gamma-activating sequence (GAS) elements and downstream STAT3 activation by inhibiting STAT1 and STAT3 dimerization in MDA-MB231 cells. Transient expression of constitutively active STAT3 significantly reduced the inhibitory effect of Poly E on cell migration and VEGF and MMP9 expression. Taken together, these observations indicate that green tea extract inhibits angiogenesis partly through the disruption of STAT3-mediated transcription of genes, including VEGF.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Breast Neoplasms / genetics
  • Breast Neoplasms / metabolism*
  • Catechin / analogs & derivatives*
  • Catechin / pharmacology*
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Endothelial Cells / drug effects
  • Endothelial Cells / metabolism
  • Enzyme Activation
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Gene Expression / drug effects
  • Gene Expression Regulation
  • Humans
  • Immunohistochemistry
  • Immunoprecipitation
  • Interferon-gamma / drug effects
  • Interferon-gamma / metabolism
  • Matrix Metalloproteinase 9 / biosynthesis
  • Matrix Metalloproteinase 9 / drug effects
  • Neovascularization, Pathologic / genetics
  • Neovascularization, Pathologic / metabolism*
  • Reverse Transcriptase Polymerase Chain Reaction
  • STAT3 Transcription Factor / drug effects*
  • STAT3 Transcription Factor / metabolism
  • Tea / chemistry*
  • Transfection
  • Vascular Endothelial Growth Factor A / biosynthesis
  • Vascular Endothelial Growth Factor A / drug effects

Substances

  • STAT3 Transcription Factor
  • STAT3 protein, human
  • Tea
  • Vascular Endothelial Growth Factor A
  • Interferon-gamma
  • Catechin
  • Matrix Metalloproteinase 9
  • polyphenon E