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

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

Author information

  • 1Center for Women's Health Research, Department of Obstetrics and Gynecology, Meharry Medical College, Nashville, Tennessee, USA.

Abstract

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.

Copyright © 2011 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

PMID:
20736132
[PubMed - indexed for MEDLINE]
PMCID:
PMC2992588
Free PMC Article

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