title: Inhibition of transcription, expression, and secretion of the vascular epithelial growth factor in human epithelial endometriotic cells by romidepsin.
abstract: OBJECTIVE
  To investigate whether the histone deacetylase (HDAC) inhibitor romidepsin down-regulates VEGF (vascular endothelial growth factor) gene expression and abrogates VEGF protein secretion in human epithelial endometriotic cells.
  
  
  METHODS
  In vitro study with human immortalized epithelial endometriotic cells.
  
  
  METHODS
  University hospital.
  
  
  METHODS
  Not applicable.
  
  
  METHODS
  None.
  
  
  METHODS
  Real-time reverse-transcriptase polymerase chain reaction to evaluate VEGF gene expression, immunoblot analysis to evaluate protein expression, and enzyme-linked immunosorbent assay to evaluate VEGF protein secretion into the culture medium.
  
  
  RESULTS
  Treatment of 11z human endometriotic cells with romidepsin statistically significantly inhibited VEGF gene transcription and down-regulated VEGF protein expression. Moreover, romidepsin abrogated the secretion of VEGF protein into the culture medium. Romidepsin also reduced the expression of hypoxia-inducible factor-1α (HIF-1α), which is implicated in the transcription of the VEGF gene, in cobalt chloride-pretreated (to mimic hypoxic conditions) 11z cultures.
  
  
  CONCLUSIONS
  Romidepsin targets VEGF at the transcriptional level, which subsequently leads to the reduction of secreted VEGF (the "active" form of VEGF). Therefore, romidepsin may be a potential therapeutic candidate against angiogenesis in endometriosis.
authors.affiliation: Department of Gynecology, University Hospital Zurich, Zurich, Switzerland.
authors.forename: Patrick
authors.initials: P
authors.lastname: Imesch
authors.forename: Eleftherios P
authors.initials: EP
authors.lastname: Samartzis
authors.forename: Michael
authors.initials: M
authors.lastname: Schneider
authors.forename: Daniel
authors.initials: D
authors.lastname: Fink
authors.forename: André
authors.initials: A
authors.lastname: Fedier
mesh_terms: D020533:Angiogenesis Inhibitors / Q000627:therapeutic use; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D002461:Cell Line, Transformed; D047630:Depsipeptides / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects / Q000235:genetics; D004353:Drug Evaluation, Preclinical; D004715:Endometriosis / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D009389:Neovascularization, Pathologic / Q000188:drug therapy; D010532:Peritoneal Diseases / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D014158:Transcription, Genetic / Q000187:drug effects / Q000502:physiology; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics* / Q000378:metabolism*
chemical_list: D020533:Angiogenesis Inhibitors; D000903:Antibiotics, Antineoplastic; D047630:Depsipeptides; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C087123:romidepsin