Anti-proliferative activity of 25-hydroxyvitamin D-3 in human prostate cells

作者：Munetsuna Eiji; Kawanami Rie; Nishikawa Miyu; Ikeda Shinnosuke; Nakabayashi Sachie; Yasuda Kaori; Ohta Miho; Kamakura Masaki; Ikushiro Shinichi; Sakaki Toshiyuki^*

来源：Molecular and Cellular Endocrinology, 2014, 382(2): 960-970.

DOI：10.1016/j.mce.2013.11.014

• Anti-proliferative activity
• Vitamin D-3
• Vitamin D receptor
• Prostate
• CYP24A1

1 alpha-Hydroxylation of 25-hydroxyvitamin D-3 is believed to be essential for its biological effects. In this study, we evaluated the biological activity of 25(OH)D-3 itself comparing with the effect of cell-derived 1 alpha,25-dihydroxyvitamin D-3 (1 alpha,25(OH)(2)D-3). First, we measured the cell-derived 1 alpha,25(OH)(2)D-3 level in immortalized human prostate cell (PZ-HPV-7) using [H-3-25(OH)D-3. The effects of the cell-derived 1 alpha,25(OH)(2)D-3 on vitamin D-3 24-hydroxylase (CYP24A1) mRNA level and the cell growth inhibition were significantly lower than the effects of 25(OH)D-3 itself added to cell culture. 25-Hydroxyvitamin D-3 1 alpha-hydroxylase (CYP27B1) gene knockdown had no significant effects on the 25(OH)D-3-dependent effects, whereas vitamin D receptor (VDR) gene knockdown resulted in a significant decrease in the 25(OH)D(3)dependent effects. These results strongly suggest that 25(OH)D-3 can directly bind to VDR and exerts its biological functions. DNA microarray and real-time RT-PCR analyses suggest that sernaphorin 3B, cystatin E/M, and cystatin D may be involved in the antiproliferative effect of 25(OH)D-3.

• 出版日期2014-2-15