Document Detail


Vitamin D inhibits proliferation of human uterine leiomyoma cells via catechol-O-methyltransferase.
MedLine Citation:
PMID:  20736132     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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
Publication Detail:
Type:  In Vitro; Journal Article; Research Support, N.I.H., Extramural     Date:  2010-08-23
Journal Detail:
Title:  Fertility and sterility     Volume:  95     ISSN:  1556-5653     ISO Abbreviation:  Fertil. Steril.     Publication Date:  2011 Jan 
Date Detail:
Created Date:  2010-12-20     Completed Date:  2011-01-21     Revised Date:  2014-09-17    
Medline Journal Info:
Nlm Unique ID:  0372772     Medline TA:  Fertil Steril     Country:  United States    
Other Details:
Languages:  eng     Pagination:  247-53     Citation Subset:  IM    
Copyright Information:
Copyright © 2011 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.
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MeSH Terms
Descriptor/Qualifier:
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
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
Grant Support
ID/Acronym/Agency:
1 R01 HD046228-01/HD/NICHD NIH HHS; G12 RR003032/RR/NCRR NIH HHS; G12 RR003032-245469/RR/NCRR NIH HHS; G12 RR003032-255421/RR/NCRR NIH HHS; G12 RR03032/RR/NCRR NIH HHS; P20 RR011792/RR/NCRR NIH HHS; P20 RR011792-10S17176/RR/NCRR NIH HHS; P20 RR011792-10S26908/RR/NCRR NIH HHS; R01 HD046228/HD/NICHD NIH HHS; R01 HD046228-08/HD/NICHD NIH HHS
Chemical
Reg. No./Substance:
0/Apoptosis Regulatory Proteins; 0/BCL2L2 protein, human; 0/Proliferating Cell Nuclear Antigen; 0/Proto-Oncogene Proteins c-bcl-2; 0/Vitamins; 1406-16-2/Vitamin D; EC 2.1.1.6/Catechol O-Methyltransferase; EC 2.7.11.22/CDC2 Protein Kinase; EC 2.7.11.24/Extracellular Signal-Regulated MAP Kinases
Comments/Corrections

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