Human prostate cells synthesize 1,25-dihydroxyvitamin D3 from 25- hydroxyvitamin D3

作者: Michael F. Holick , Lyman W. Whitlatch , Balakrishna L Lokeshwar , Tai C. Chen , Gary G. Schwartz

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摘要: Epidemiological and laboratory data support a role for vitamin D in the growth differentiation of human prostatic cells. These findings prompted us to ask whether cells could convert 25-hydroxyvitamin D3 (25-OH-D3), major circulating metabolite D3, 1,25-dihydroxyvitamin [1,25(OH)2D3], hormonally active metabolite, manner similar cultured keratinocytes. Therefore, we investigated three well-characterized prostate cancer cell lines, LNCaP, DU 145, PC-3; two primary cultures derived from noncancerous prostates (one normal one benign hyperplasia); keratinocytes their ability synthesize 1,25(OH)2D3. Assays were performed presence 25-OH-D3 as enzyme substrate 1,2-dianilinoethane, an antioxidant free radical scavenger, absence clotrimazole, cytochrome P450 inhibitor. 145 PC-3 produced 0.31 +/- 0.06 0.07 0.01 pmol 1,25(OH)2D3/mg protein/h, respectively. No measurable 1,25(OH)2D3 was detected LNCaP The hyperplasia keratinocyte 3.08 1.56, 1.05 0.31, 2.1 0.1 respectively, using calf thymus receptor binding assay measure 1,2-dianilinoethane. identity analyte supported by high performance liquid chromatography [3H]25-OH-D3 solvent system that is specific production lines completely inhibited clotrimazole. This report demonstrates well cells, possess 1alpha-hydroxylase activity can 25-OH-D3. Together with recent indicating inhibits invasiveness (G. G. Schwartz et al., Cancer Epidemiol. Biomark. Prev., 6: 727-732, 1997), these suggest potential chemoprevention invasive cancer.

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