title: Berberine inhibits the proliferation of human uterine leiomyoma cells.
abstract: OBJECTIVE
  To determine whether berberine (BBR), a naturally occurring plant-derived alkaloid, inhibits the proliferation of human uterine leiomyoma (UtLM) cells.
  
  
  METHODS
  Laboratory research.
  
  
  METHODS
  Laboratory.
  
  
  METHODS
  UtLM and normal human uterine smooth muscle (UtSMC) cell lines.
  
  
  METHODS
  Treatment with [1] BBR (10, 20, and 50 μM), [2] BBR (20 and 50 μM) and/or 17β-estradiol (E2; 10 and 100 nM), and [3] BBR (20 and 50 μM) and/or progesterone (P4; 10 and 100 nM) for 24 or 72 hours.
  
  
  METHODS
  Cell proliferation, cell cycle, apoptosis, and related genes expression were determined.
  
  
  RESULTS
  BBR inhibited UtLM cell proliferation by inducing G2/M cell cycle arrest and apoptosis. Cell cycle G2/M phase-related genes were altered by BBR treatment: the expression of cyclin A1, cyclin B1, and Cdk1 were down-regulated, while Cdk4, p21, and p53 were up-regulated. BBR-treated cells stained positively for annexin V and manifested increased BAX expression. E2- and P4-induced UtLM cell proliferation was blocked by BBR treatment. In marked contrast, even the highest concentration of BBR (50 μM) did not influence cell proliferation in UtSMC cells.
  
  
  CONCLUSIONS
  BBR selectively inhibits cellular proliferation and blocks E2- and P4-induced cell proliferation in UtLM but not in normal UtSMC cells. In addition, BBR did not demonstrate cytotoxicity effects in normal human UtSMCs. Our results suggest BBR could be a potential therapeutic agent for the treatment of uterine leiomyoma.
authors: Department of Obstetrics and Gynecology, Georgia Regents University, Augusta, Georgia.
authors: Hsiao-Li
authors: HL
authors: Wu
authors: Department of Obstetrics and Gynecology, Georgia Regents University, Augusta, Georgia.
authors: Tung-Yueh
authors: TY
authors: Chuang
authors: Department of Obstetrics and Gynecology, Georgia Regents University, Augusta, Georgia.
authors: Ayman
authors: A
authors: Al-Hendy
authors: Department of Obstetrics and Gynecology, Georgia Regents University, Augusta, Georgia.
authors: Michael P
authors: MP
authors: Diamond
authors: Department of Obstetrics and Gynecology, Georgia Regents University, Augusta, Georgia; Department of Medicine, Georgia Regents University, Augusta, Georgia.
authors: Ricardo
authors: R
authors: Azziz
authors: Department of Obstetrics and Gynecology, Georgia Regents University, Augusta, Georgia. Electronic address: yechen@gru.edu.
authors: Yen-Hao
authors: YH
authors: Chen
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology* / Q000627:therapeutic use; D001599:Berberine / Q000494:pharmacology* / Q000627:therapeutic use; D049109:Cell Proliferation / Q000187:drug effects*; D004336:Drug Antagonism; D004958:Estradiol / Q000494:pharmacology; D004965:Estrogen Antagonists / Q000494:pharmacology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D007889:Leiomyoma / Q000188:drug therapy / Q000235:genetics / Q000473:pathology*; D011374:Progesterone / Q000037:antagonists & inhibitors / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D014594:Uterine Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000473:pathology*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D004965:Estrogen Antagonists; D001599:Berberine; D011374:Progesterone; D004958:Estradiol
keywords: Berberine; anti-tumorigenic; antineoplastic; fibroids; leiomyomas; treatment; uterus