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

Chakradhari Sharan, Sunil Krishna Halder, Chandrasekhar Thota, Tarannum Jaleel, Sangeeta Nair, Ayman Al-Hendy

Research output: Contribution to journalArticle

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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.

Original languageEnglish (US)
Pages (from-to)247-253
Number of pages7
JournalFertility and sterility
Volume95
Issue number1
DOIs
StatePublished - Jan 1 2011

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Catechol O-Methyltransferase
Leiomyoma
Vitamin D
Proliferating Cell Nuclear Antigen
Cell Proliferation
Reverse Transcription
Western Blotting
CDC2 Protein Kinase
Polymerase Chain Reaction
Somatostatin-Secreting Cells
Calcitriol
Extracellular Signal-Regulated MAP Kinases
Enzyme Assays
Enzymes
Growth
Human Activities
Down-Regulation
High Pressure Liquid Chromatography
Outcome Assessment (Health Care)
Messenger RNA

Keywords

  • COMT
  • Vitamin D
  • catechol-O-methyltransferase
  • hypovitaminosis D
  • proliferation
  • uterine leiomyoma

ASJC Scopus subject areas

  • Obstetrics and Gynecology
  • Reproductive Medicine

Cite this

Vitamin D inhibits proliferation of human uterine leiomyoma cells via catechol-O-methyltransferase. / Sharan, Chakradhari; Halder, Sunil Krishna; Thota, Chandrasekhar; Jaleel, Tarannum; Nair, Sangeeta; Al-Hendy, Ayman.

In: Fertility and sterility, Vol. 95, No. 1, 01.01.2011, p. 247-253.

Research output: Contribution to journalArticle

Sharan, Chakradhari ; Halder, Sunil Krishna ; Thota, Chandrasekhar ; Jaleel, Tarannum ; Nair, Sangeeta ; Al-Hendy, Ayman. / Vitamin D inhibits proliferation of human uterine leiomyoma cells via catechol-O-methyltransferase. In: Fertility and sterility. 2011 ; Vol. 95, No. 1. pp. 247-253.
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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.",
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AU - Thota, Chandrasekhar

AU - Jaleel, Tarannum

AU - Nair, Sangeeta

AU - Al-Hendy, Ayman

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AB - 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.

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