title: Antifibrotic properties of epigallocatechin-3-gallate in endometriosis.
abstract: OBJECTIVE
  Is epigallocatechin-3-gallate (EGCG) treatment effective in the treatment of fibrosis in endometriosis?
  
  
  CONCLUSIONS
  EGCG appears to have antifibrotic properties in endometriosis.
  
  
  BACKGROUND
  Histologically, endometriosis is characterized by dense fibrous tissue surrounding the endometrial glands and stroma. However, only a few studies to date have evaluated candidate new therapies for endometriosis-associated fibrosis.
  
  
  METHODS
  For this laboratory study, samples from 55 patients (45 with and 10 without endometriosis) of reproductive age with normal menstrual cycles were analyzed. A total of 40 nude mice received single injection proliferative endometrial fragments from a total of 10 samples.
  
  
  METHODS
  The in vitro effects of EGCG and N-acetyl-l-cysteine on fibrotic markers (alpha-smooth muscle actin, type I collagen, connective tissue growth factor and fibronectin) with and without transforming growth factor (TGF)-β1 stimulation, as well as on cell proliferation, migration and invasion and collagen gel contraction of endometrial and endometriotic stromal cells were evaluated by real-time PCR, immunocytochemistry, cell proliferation assays, in vitro migration and invasion assays and/or collagen gel contraction assays. The in vitro effects of EGCG on mitogen-activated protein kinase (MAPK) and Smad signaling pathways in endometrial and endometriotic stromal cells were evaluated by western blotting. Additionally, the effects of EGCG treatment on endometriotic implants were evaluated in a xenograft model of endometriosis in immunodeficient nude mice.
  
  
  RESULTS
  Treatment with EGCG significantly inhibited cell proliferation, migration and invasion of endometrial and endometriotic stromal cells from patients with endometriosis. In addition, EGCG treatment significantly decreased the TGF-β1-dependent increase in the mRNA expression of fibrotic markers in both endometriotic and endometrial stromal cells. Both endometriotic and endometrial stromal cell-mediated contraction of collagen gels were significantly attenuated at 8, 12 and 24 h after treatment with EGCG. Epigallocatechin-3-gallate also significantly inhibited TGF-β1-stimulated activation of MAPK and Smad signaling pathways in endometrial and endometriotic stromal cells. Animal experiments showed that EGCG prevented the progression of fibrosis in endometriosis.
  
  
  CONCLUSIONS
  The attractiveness of epigallocatechin-3-gallate as a drug candidate has been diminished by its relatively low bioavailability. However, numerous alterations to the EGCG molecule have been patented, either to improve the integrity of the native compound or to generate a more stable yet similarly efficacious molecule. Therefore, EGCG and its derivatives, analogs and prodrugs could potentially be developed into agents for the future treatment and/or prevention of endometriosis.
  
  
  CONCLUSIONS
  Epigallocatechin-3-gallate is a potential drug candidate for the treatment and/or prevention of endometriosis.
  
  
  BACKGROUND
  This study was supported in part by Karl Storz Endoscopy & GmbH (Tuttlingen, Germany). No competing interests are declared.
authors.affiliation: CHU Clermont-Ferrand, CHU Estaing, Chirurgie Gynécologique, 1, Place Lucie Aubrac, 63003 Clermont-Ferrand, France Clermont Université, Université d'Auvergne, ISIT UMR6284, Clermont-Ferrand, France CNRS, ISIT UMR6284, Clermont-Ferrand, France sachikoma@aol.com.
authors.forename: Sachiko
authors.initials: S
authors.lastname: Matsuzaki
authors.affiliation: CHU Clermont-Ferrand, Service d'Anatomie et Cytologie Pathologiques, Clermont-Ferrand, France.
authors.forename: Claude
authors.initials: C
authors.lastname: Darcha
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology*; D000199:Actins / Q000378:metabolism; D000328:Adult; D000818:Animals; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D055513:Connective Tissue Growth Factor / Q000378:metabolism; D004715:Endometriosis / Q000188:drug therapy / Q000473:pathology*; D005260:Female; D005353:Fibronectins / Q000378:metabolism; D005355:Fibrosis / Q000188:drug therapy; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D010446:Peptide Fragments / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000199:Actins; C526317:CCN2 protein, human; D005353:Fibronectins; D010446:Peptide Fragments; D055513:Connective Tissue Growth Factor; D002392:Catechin; C045651:epigallocatechin gallate; C471083:Col-1 peptide, human; D020778:Matrix Metalloproteinase 2; D000111:Acetylcysteine
keywords: endometriosis; endometrium; epigallocatechin-3-gallate; fibrosis