Vitamin D Metabolism in Human Prostate Cells: Implications for Prostate Cancer Chemoprevention by Vitamin D

Abstract

Background: Prostate cells can produce 1α,25-dihydroxyvitamin D₃ (1α,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 1α,25(OH)₂D₃ were investigated. Materials and Methods: Protein and receptor binding assays were used to determine 25(OH)D₃ and 1α,25(OH)₂D₃, respectively. Measurements of proliferation by ³H-thymidine incorporation, and 1α,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 1α,25(OH)₂D₃. Vitamin D₃ up-regulated 25(OH)D-24R-hydroxylase and IGFBP3, two 1α,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 1α,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.