title: Inhibition of canonical WNT signaling attenuates human leiomyoma cell growth.
abstract: OBJECTIVE
  To assess the effect of three WNT/β-catenin pathway inhibitors-inhibitor of β-catenin and TCF4 (ICAT), niclosamide, and XAV939-on the proliferation of primary cultures of human uterine leiomyoma cells.
  
  
  METHODS
  Prospective study of human leiomyoma cells obtained from myomectomy or hysterectomy.
  
  
  METHODS
  University research laboratory.
  
  
  METHODS
  Women (n = 38) aged 27-53 years undergoing surgery.
  
  
  METHODS
  Adenoviral ICAT overexpression or treatment with varying concentrations of niclosamide or XAV939.
  
  
  METHODS
  Cell proliferation, cell death, WNT/-catenin target gene expression or reporter gene regulation, β-catenin levels, and cellular localization.
  
  
  RESULTS
  Inhibitor of β-catenin and TCF4, niclosamide, or XAV939 inhibit WNT/β-catenin pathway activation and exert antiproliferative effects in primary cultures of human leiomyoma cells.
  
  
  CONCLUSIONS
  Three WNT/-catenin pathway inhibitors specifically block human leiomyoma growth and proliferation, suggesting that the canonical WNT pathway may be a potential therapeutic target for the treatment of uterine leiomyoma. Our findings provide rationale for further preclinical and clinical evaluation of ICAT, niclosamide, and XAV939 as candidate antitumor agents for uterine leiomyoma.
authors.affiliation: Department of Obstetrics and Gynecology, Feinberg School of Medicine at Northwestern University, Chicago, Illinois.
authors.forename: Masanori
authors.initials: M
authors.lastname: Ono
authors.affiliation: Department of Obstetrics and Gynecology, Feinberg School of Medicine at Northwestern University, Chicago, Illinois.
authors.forename: Ping
authors.initials: P
authors.lastname: Yin
authors.affiliation: Department of Obstetrics and Gynecology, Feinberg School of Medicine at Northwestern University, Chicago, Illinois.
authors.forename: Antonia
authors.initials: A
authors.lastname: Navarro
authors.affiliation: Department of Obstetrics and Gynecology, Feinberg School of Medicine at Northwestern University, Chicago, Illinois.
authors.forename: Molly B
authors.initials: MB
authors.lastname: Moravek
authors.affiliation: Department of Obstetrics and Gynecology, Feinberg School of Medicine at Northwestern University, Chicago, Illinois.
authors.forename: John S
authors.initials: JS
authors.lastname: Coon V
authors.affiliation: Department of Obstetrics and Gynecology, Feinberg School of Medicine at Northwestern University, Chicago, Illinois.
authors.forename: Stacy A
authors.initials: SA
authors.lastname: Druschitz
authors.affiliation: Department of Medicine, Feinberg School of Medicine at Northwestern University, Chicago, Illinois.
authors.forename: Cara J
authors.initials: CJ
authors.lastname: Gottardi
authors.affiliation: Department of Obstetrics and Gynecology, Feinberg School of Medicine at Northwestern University, Chicago, Illinois. Electronic address: Sbulun@nmh.org.
authors.forename: Serdar E
authors.initials: SE
authors.lastname: Bulun
mesh_terms: D000328:Adult; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D006575:Heterocyclic Compounds, 3-Ring / Q000494:pharmacology; D006801:Humans; D007889:Leiomyoma / Q000378:metabolism* / Q000473:pathology* / Q000517:prevention & control; D008875:Middle Aged; D009534:Niclosamide / Q000494:pharmacology; D011446:Prospective Studies; D014407:Tumor Cells, Cultured; D014594:Uterine Neoplasms / Q000378:metabolism* / Q000473:pathology* / Q000517:prevention & control; D051153:Wnt Proteins / Q000037:antagonists & inhibitors* / Q000502:physiology*; D060449:Wnt Signaling Pathway / Q000187:drug effects / Q000502:physiology*
chemical_list: D006575:Heterocyclic Compounds, 3-Ring; D051153:Wnt Proteins; C544261:XAV939; D009534:Niclosamide
keywords: Leiomyoma; WNT/β-catenin; XAV939; niclosamide; tumor biology