title: Green tea epigallocatechin-3-gallate inhibits angiogenesis and suppresses vascular endothelial growth factor C/vascular endothelial growth factor receptor 2 expression and signaling in experimental endometriosis in vivo.
abstract: OBJECTIVE
  To investigate the antiangiogenesis mechanism of epigallocatechin-3-gallate (EGCG) in an endometriosis model in vivo.
  
  
  METHODS
  Animal studies.
  
  
  METHODS
  University laboratory.
  
  
  METHODS
  Human endometrium from women with endometriosis (n = 10) was transplanted into immunocompromised mice.
  
  
  METHODS
  Mice (n = 30) were randomly treated with EGCG, vitamin E (antioxidant control), or vehicle (negative control) for microvessel imaging.
  
  
  METHODS
  Endometriotic implants were collected for angiogenesis microarray and pathway analysis. Differentially expressed angiogenesis molecules were confirmed by quantitative polymerase chain reaction, Western blot, and immunohistochemistry. Effects of EGCG on angiogenesis signal transduction were further characterized in a human endothelial cell line. Microvessel parameters and the angiogenesis signaling pathway in endometriotic implants and endothelial cells were studied.
  
  
  RESULTS
  EGCG, but not vitamin E, inhibited microvessels in endometriotic implants. EGCG selectively suppressed vascular endothelial growth factor C (VEGFC) and tyrosine kinase receptor VEGF receptor 2 (VEGFR2) expression. EGCG down-regulated VEGFC/VEGFR2 signaling through c-JUN, interferon-γ, matrix metalloproteinase 9, and chemokine (C-X-C motif) ligand 3 pathways for endothelial proliferation, inflammatory response, and mobility. EGCG also suppressed VEGFC expression and reduced VEGFR2 and ERK activation in endothelial cells. VEGFC supplementation attenuated the inhibitory effects by EGCG.
  
  
  CONCLUSIONS
  EGCG inhibited angiogenesis and suppressed VEGFC/VEGFR2 expression and signaling pathway in experimental endometriosis in vivo and endothelial cells in vitro.
authors.affiliation: Department of Obstetrics and Gynaecology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, New Territories, Hong Kong.
authors.forename: Hui
authors.initials: H
authors.lastname: Xu
authors.forename: Christian M
authors.initials: CM
authors.lastname: Becker
authors.forename: Wai Ting
authors.initials: WT
authors.lastname: Lui
authors.forename: Ching Yan
authors.initials: CY
authors.lastname: Chu
authors.forename: Tina N
authors.initials: TN
authors.lastname: Davis
authors.forename: Andrew L
authors.initials: AL
authors.lastname: Kung
authors.forename: Amy E
authors.initials: AE
authors.lastname: Birsner
authors.forename: Robert J
authors.initials: RJ
authors.lastname: D'Amato
authors.forename: Gene Chi
authors.initials: GC
authors.lastname: Wai Man
authors.forename: Chi Chiu
authors.initials: CC
authors.lastname: Wang
mesh_terms: D000328:Adult; D000818:Animals; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D002478:Cells, Cultured; D004715:Endometriosis / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D009389:Neovascularization, Pathologic / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D011897:Random Allocation; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D013662:Tea; D042582:Vascular Endothelial Growth Factor C / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000502:physiology
chemical_list: D013662:Tea; D042582:Vascular Endothelial Growth Factor C; D002392:Catechin; C045651:epigallocatechin gallate; D040301:Vascular Endothelial Growth Factor Receptor-2