title: Vitamin D inhibits proliferation of human uterine leiomyoma cells via catechol-O-methyltransferase.
abstract: OBJECTIVE
  To evaluate the effects and mechanisms of action of vitamin D on human uterine leiomyoma (HuLM) cell proliferation in vitro.
  
  
  METHODS
  Laboratory study.
  
  
  METHODS
  University hospitals.
  
  
  METHODS
  Not applicable.
  
  
  METHODS
  Not applicable.
  
  
  METHODS
  HuLM cells were treated with 1,25-dihydroxyvitamin D3 (vitamin D), and cell proliferation was assayed by the methylthiazolyl tetrazolium technique. proliferating cell nuclear antigen (PCNA), BCL-2, BCL-w, cyclin-dependent kinase (CDK) 1, and catechol-O-methyltransferase (COMT) protein levels were analyzed by Western blotting. COMT mRNA and enzyme activity were assayed by quantitative reverse-transcription polymerase chain reaction (RT-PCR) and high-performance liquid chromatography analysis, respectively. The role of COMT was evaluated in stable HuLM cells by silencing COMT expression.
  
  
  RESULTS
  Vitamin D inhibited the growth of HuLM cells by 47±0.03% at 1 μM and by 38±0.02% at 0.1 μM compared with control cells at 120 hours of treatment. Vitamin D inhibited extracellular signal-regulated kinase activation and down-regulated the expression of BCL-2, BCL-w, CDK1, and PCNA. Western blot, RT-PCR, and enzyme assay of COMT demonstrated inhibitory effects of vitamin D on COMT expression and enzyme activity. Silencing endogenous COMT expression abolished vitamin D-mediated inhibition of HuLM cell proliferation.
  
  
  CONCLUSIONS
  Vitamin D inhibits growth of HuLM cells through the down-regulation of PCNA, CDK1, and BCL-2 and suppresses COMT expression and activity in HuLM cells. Thus, hypovitaminosis D appears to be a risk factor for uterine fibroids.
authors.affiliation: Center for Women's Health Research, Department of Obstetrics and Gynecology, Meharry Medical College, Nashville, Tennessee, USA.
authors.forename: Chakradhari
authors.initials: C
authors.lastname: Sharan
authors.forename: Sunil K
authors.initials: SK
authors.lastname: Halder
authors.forename: Chandrasekhar
authors.initials: C
authors.lastname: Thota
authors.forename: Tarannum
authors.initials: T
authors.lastname: Jaleel
authors.forename: Sangeeta
authors.initials: S
authors.lastname: Nair
authors.forename: Ayman
authors.initials: A
authors.lastname: Al-Hendy
mesh_terms: D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D016203:CDC2 Protein Kinase / Q000378:metabolism; D002394:Catechol O-Methyltransferase / Q000235:genetics / Q000378:metabolism*; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D004789:Enzyme Activation / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D007889:Leiomyoma / Q000188:drug therapy* / Q000453:epidemiology / Q000473:pathology; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D012307:Risk Factors; D014594:Uterine Neoplasms / Q000188:drug therapy* / Q000453:epidemiology / Q000473:pathology; D014807:Vitamin D / Q000494:pharmacology*; D014808:Vitamin D Deficiency / Q000453:epidemiology; D014815:Vitamins / Q000494:pharmacology
chemical_list: D051017:Apoptosis Regulatory Proteins; C491073:BCL2L2 protein, human; D018809:Proliferating Cell Nuclear Antigen; D019253:Proto-Oncogene Proteins c-bcl-2; D014815:Vitamins; D014807:Vitamin D; D002394:Catechol O-Methyltransferase; D016203:CDC2 Protein Kinase; D048049:Extracellular Signal-Regulated MAP Kinases