title: Green tea catechins inhibit angiogenesis through suppression of STAT3 activation.
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.
authors.affiliation: The Ben May Department for Cancer Research, The University of Chicago, GCIS W325D, 929 East 57th Street, Chicago, IL 60637, USA. leong@uhc.edu
authors.forename: Hoyee
authors.initials: H
authors.lastname: Leong
authors.forename: Priya S
authors.initials: PS
authors.lastname: Mathur
authors.forename: Geoffrey L
authors.initials: GL
authors.lastname: Greene
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism*; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D004789:Enzyme Activation; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D005786:Gene Expression Regulation; D006801:Humans; D007150:Immunohistochemistry; D047468:Immunoprecipitation; D007371:Interferon-gamma / Q000187:drug effects / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis / Q000187:drug effects; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050796:STAT3 Transcription Factor / Q000187:drug effects* / Q000378:metabolism; D013662:Tea / Q000737:chemistry*; D014162:Transfection; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis / Q000187:drug effects
chemical_list: D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D013662:Tea; D042461:Vascular Endothelial Growth Factor A; D007371:Interferon-gamma; D002392:Catechin; D020780:Matrix Metalloproteinase 9; C472086:polyphenon E