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.

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.

• Authors: Chakradhari Sharan, Sunil K Halder, Chandrasekhar Thota, Tarannum Jaleel, Sangeeta Nair, Ayman Al-Hendy
• Journal: Fertility and sterility (Fertil Steril) Vol. 95 Issue 1 Pg. 247-53 (Jan 2011) ISSN: 1556-5653 [Electronic] United States
• PMID: 20736132 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
• Copyright: Copyright © 2011 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Chemical References

• 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

Topics

• Apoptosis Regulatory Proteins (metabolism)
• CDC2 Protein Kinase (metabolism)
• Catechol O-Methyltransferase (genetics, 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, epidemiology, pathology)
• Proliferating Cell Nuclear Antigen (metabolism)
• Proto-Oncogene Proteins c-bcl-2 (metabolism)
• Risk Factors
• Uterine Neoplasms (drug therapy, epidemiology, pathology)
• Vitamin D (pharmacology)
• Vitamin D Deficiency (epidemiology)
• Vitamins (pharmacology)