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

ObjectiveTo evaluate the effects and mechanisms of action of vitamin D on human uterine leiomyoma (HuLM) cell proliferation in vitro.DesignLaboratory study.SettingUniversity 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.