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

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• 作者：Eiji Munetsuna ; Rie Kawanami ; Miyu Nishikawa ; Shinnosuke Ikeda ; Sachie Nakabayashi ; Kaori Yasuda ; Miho Ohta ; Masaki Kamakura ; Shinichi Ikushiro ; Toshiyuki Sakaki
• 关键词：25(OH) D3 ; 25-hydroxyvitamin D3 ; 1伪 ; 25(OH)2D3 ; 1伪 ; 25-dihydroxyvitamin D3 ; 1伪 ; 25(OH)2D3 ; 1伪 ; 25-dihydroxy vitamin D3 ; HPLC ; high performance liquid chromatography ; LC&ndash ; MS ; liquid chromatography mass spectroscopy ; VDR ; vitamin D receptor ; RXR ; retinoid X receptor ; GAPDH ; glyceraldehyde-3-phosphate dehydrogenase ; BPE ; bovine pituitary extract ; siRNA ; small interfering RNA
• 刊名：Molecular and Cellular Endocrinology
• 出版年：15 February, 2014
• 年：2014
• 卷：382
• 期：2
• 页码：960-970
• 全文大小：930 K

文摘

1伪-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 1伪,25-dihydroxyvitamin D₃ (1伪,25(OH)₂D₃). First, we measured the cell-derived 1伪,25(OH)₂D₃ level in immortalized human prostate cell (PZ-HPV-7) using [³H]-25(OH)D₃. The effects of the cell-derived 1伪,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 1伪-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.