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

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.

The prostate 25-hydroxyvitamin D-1 alpha-hydroxylase is not influenced by parathyroid hormone and calcium: implications for prostate cancer chemoprevention by vitamin D.

The hormonal form of vitamin D, 1 alpha,25-dihydroxyvitamin D [1 alpha,25(OH)(2)D] promotes the differentiation and inhibits the proliferation, invasiveness and metastasis of prostate cells. However, 1 alpha,25(OH)(2)D is not suitable as a chemopreventive agent because its administration can cause hypercalcemia. Serum levels of 1 alpha,25(OH)(2)D are tightly regulated by the renal enzyme, 25-hydroxyvitamin D-1 alpha-hydroxylase (1 alpha-OHase), which synthesizes 1 alpha,25(OH)(2)D from the prohormone, 25-hydroxyvitamin D [25(OH)D].

25-Hydroxyvitamin D-1alpha-hydroxylase activity is diminished in human prostate cancer cells and is enhanced by gene transfer.

The hormone 1alpha,25-dihydroxyvitamin D (1alpha,25(OH)(2)D) inhibits growth and induces differentiation of prostate cells. The enzyme responsible for 1alpha,25(OH)(2)D synthesis, 25-hydroxyvitamin D (25(OH)D)-1alpha-hydroxylase (1alpha-OHase), has been demonstrated in human prostate cells. We compared the levels of 1alpha-OHase activity in prostate cancer cell lines, LNCaP, DU145 and PC-3 and in primary cultures of normal, cancerous and benign prostatic hyperplasia (BPH) prostate cells.