Vitamin D metabolism in human prostate cells: implications for prostate cancer chemoprevention by vitamin D.

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Flanagan JN, Young MV, Persons KS, Wang L, Mathieu JS, Whitlatch LW, Holick MF, Chen TC

Vitamin D metabolism in human prostate cells: implications for prostate cancer chemoprevention by vitamin D.

Anticancer Res. 2006 Jul-Aug;26(4A):2567-72.

PubMed ID

16886665 [ View in PubMed

]

Abstract

BACKGROUND: Prostate cells can produce 1alpha,25-dihydroxyvitamin D3 (1alpha,25(OH)2D3) from 25-hydroxyvitamin D3 (25(OH)D3) to regulate their own growth. Here, the questions of whether prostate cells express vitamin D-25-hydroxylase (25-OHase) and can convert vitamin D3 to 1alpha,25(OH)2D3 were investigated. MATERIALS AND METHODS: Protein and receptor binding assays were used to determine 25(OH)D3 and 1alpha,25(OH)2D3, respectively. Measurements of proliferation by 3H-thymidine incorporation, and 1alpha,25(OH)2D-responsive gene expression by real-time qPCR and by Western blot were used as functional assays for the presence of 25-OHase activity. RESULTS: Prostate cells metabolized vitamin D3 to 1alpha,25(OH)2D3. Vitamin D3 up-regulated 25(OH)D-24R-hydroxylase and IGFBP3, two 1alpha,25(OH)2D-responsive genes, in prostate cells. CYP2R1 was the major form of 25-OHase expressed in normal and cancerous prostate cells as determined by qPCR. CONCLUSION: The autocrine synthesis of 1alpha,25(OH)2D3 from vitamin D3 suggests that maintaining adequate levels of serum vitamin D could be a safe and effective chemo-preventive measure to decrease the risk of prostate cancer.

DrugBank Data that Cites this Article

Drug Enzymes

Drug	Enzyme	Kind	Organism	Pharmacological Action	Actions
Cholecalciferol	Vitamin D 25-hydroxylase	Protein	Humans	Unknown	Substrate	Details