Vitamin D inhibits proliferation of human uterine leiomyoma cells via catechol-O-methyltransferase

Fertil Steril. 2011 Jan;95(1):247-53. doi: 10.1016/j.fertnstert.2010.07.1041. Epub 2010 Aug 23.


Objective: To evaluate the effects and mechanisms of action of vitamin D on human uterine leiomyoma (HuLM) cell proliferation in vitro.

Design: Laboratory study.

Setting: University hospitals.

Patients(s): Not applicable.

Interventions(s): Not applicable.

Main outcome measure(s): 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.

Result(s): 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.

Conclusion(s): 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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Apoptosis Regulatory Proteins / metabolism
  • CDC2 Protein Kinase / metabolism
  • Catechol O-Methyltransferase / genetics
  • Catechol O-Methyltransferase / metabolism*
  • Cell Division / drug effects
  • Cell Line, Tumor
  • Enzyme Activation / drug effects
  • Extracellular Signal-Regulated MAP Kinases / metabolism
  • Female
  • Gene Expression Regulation, Enzymologic / drug effects
  • Humans
  • In Vitro Techniques
  • Leiomyoma / drug therapy*
  • Leiomyoma / epidemiology
  • Leiomyoma / pathology
  • Proliferating Cell Nuclear Antigen / metabolism
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Risk Factors
  • Uterine Neoplasms / drug therapy*
  • Uterine Neoplasms / epidemiology
  • Uterine Neoplasms / pathology
  • Vitamin D / pharmacology*
  • Vitamin D Deficiency / epidemiology
  • Vitamins / pharmacology


  • Apoptosis Regulatory Proteins
  • BCL2L2 protein, human
  • Proliferating Cell Nuclear Antigen
  • Proto-Oncogene Proteins c-bcl-2
  • Vitamins
  • Vitamin D
  • Catechol O-Methyltransferase
  • CDC2 Protein Kinase
  • Extracellular Signal-Regulated MAP Kinases