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Anti-proliferative activity of 25-hydroxyvitamin D3 in human prostate cells

Munetsuna, Eiji, Kawanami, Rie, Nishikawa, Miyu, Ikeda, Shinnosuke, Nakabayashi, Sachie, Yasuda, Kaori, Ohta, Miho, Kamakura, Masaki, Ikushiro, Shinichi, Sakaki, Toshiyuki
Molecular and Cellular Endocrinology 2014 v.382 pp. 960-970
25-hydroxycholecalciferol, DNA microarrays, bioactive properties, cell culture, cell growth, gene expression, genes, humans, messenger RNA, quantitative polymerase chain reaction, reverse transcriptase polymerase chain reaction
1α-Hydroxylation of 25-hydroxyvitamin D3 is believed to be essential for its biological effects. In this study, we evaluated the biological activity of 25(OH)D3 itself comparing with the effect of cell-derived 1α,25-dihydroxyvitamin D3 (1α,25(OH)2D3). First, we measured the cell-derived 1α,25(OH)2D3 level in immortalized human prostate cell (PZ-HPV-7) using [3H]-25(OH)D3. The effects of the cell-derived 1α,25(OH)2D3 on vitamin D3 24-hydroxylase (CYP24A1) mRNA level and the cell growth inhibition were significantly lower than the effects of 25(OH)D3 itself added to cell culture. 25-Hydroxyvitamin D3 1α-hydroxylase (CYP27B1) gene knockdown had no significant effects on the 25(OH)D3-dependent effects, whereas vitamin D receptor (VDR) gene knockdown resulted in a significant decrease in the 25(OH)D3-dependent effects. These results strongly suggest that 25(OH)D3 can directly bind to VDR and exerts its biological functions. DNA microarray and real-time RT–PCR analyses suggest that semaphorin 3B, cystatin E/M, and cystatin D may be involved in the antiproliferative effect of 25(OH)D3.