Green tea catechins inhibit angiogenesis through suppression of STAT3 activation.
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.
Leong
Hoyee
H
The Ben May Department for Cancer Research, The University of Chicago, GCIS W325D, 929 East 57th Street, Chicago, IL 60637, USA. leong@uhc.edu
Mathur
Priya S
PS
Greene
Geoffrey L
GL
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
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