title: Anti-proliferative activity of 25-hydroxyvitamin D3 in human prostate cells.
abstract: 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 [(3)H]-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.
authors.affiliation: Department of Biotechnology, Faculty of Engineering, Toyama Prefectural University, 5180 Kurokawa, Imizu, Toyama 939-0398, Japan; Department of Biochemistry, Fujita Health University for Medical Science, Toyoake 470-1192, Japan.
authors.forename: Eiji
authors.initials: E
authors.lastname: Munetsuna
authors.affiliation: Department of Biotechnology, Faculty of Engineering, Toyama Prefectural University, 5180 Kurokawa, Imizu, Toyama 939-0398, Japan.
authors.forename: Rie
authors.initials: R
authors.lastname: Kawanami
authors.affiliation: Department of Biotechnology, Faculty of Engineering, Toyama Prefectural University, 5180 Kurokawa, Imizu, Toyama 939-0398, Japan.
authors.forename: Miyu
authors.initials: M
authors.lastname: Nishikawa
authors.affiliation: Department of Biotechnology, Faculty of Engineering, Toyama Prefectural University, 5180 Kurokawa, Imizu, Toyama 939-0398, Japan.
authors.forename: Shinnosuke
authors.initials: S
authors.lastname: Ikeda
authors.affiliation: Department of Biotechnology, Faculty of Engineering, Toyama Prefectural University, 5180 Kurokawa, Imizu, Toyama 939-0398, Japan.
authors.forename: Sachie
authors.initials: S
authors.lastname: Nakabayashi
authors.affiliation: Department of Biotechnology, Faculty of Engineering, Toyama Prefectural University, 5180 Kurokawa, Imizu, Toyama 939-0398, Japan.
authors.forename: Kaori
authors.initials: K
authors.lastname: Yasuda
authors.affiliation: Development Nourishment Department, Soai University, 4-4-1 Nankonaka, Suminoe, Osaka 559-0033, Japan.
authors.forename: Miho
authors.initials: M
authors.lastname: Ohta
authors.affiliation: Department of Biotechnology, Faculty of Engineering, Toyama Prefectural University, 5180 Kurokawa, Imizu, Toyama 939-0398, Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Kamakura
authors.affiliation: Department of Biotechnology, Faculty of Engineering, Toyama Prefectural University, 5180 Kurokawa, Imizu, Toyama 939-0398, Japan.
authors.forename: Shinichi
authors.initials: S
authors.lastname: Ikushiro
authors.affiliation: Department of Biotechnology, Faculty of Engineering, Toyama Prefectural University, 5180 Kurokawa, Imizu, Toyama 939-0398, Japan. Electronic address: tsakaki@pu-toyama.ac.jp.
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Sakaki
mesh_terms: D002112:Calcifediol / Q000494:pharmacology*; D002461:Cell Line, Transformed; D049109:Cell Proliferation / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D055332:Cystatin M / Q000235:genetics / Q000378:metabolism; D015891:Cystatins / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism; D011467:Prostate / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D011485:Protein Binding; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D018167:Receptors, Calcitriol / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D039961:Semaphorins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D013250:Steroid Hydroxylases / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D014316:Tritium; D065668:Vitamin D3 24-Hydroxylase
chemical_list: C525104:CST6 protein, human; D055332:Cystatin M; D015891:Cystatins; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D018167:Receptors, Calcitriol; C409766:SEMA3B protein, human; D039961:Semaphorins; D014316:Tritium; C071378:CST5 protein, human; D013250:Steroid Hydroxylases; C585549:CYP24A1 protein, human; D065668:Vitamin D3 24-Hydroxylase; D002112:Calcifediol
keywords: 1α,25(OH)(2)D(3); 1α,25-dihydroxy vitamin D(3); 1α,25-dihydroxyvitamin D(3); 25(OH) D(3); 25-hydroxyvitamin D(3); Anti-proliferative activity; BPE; CYP24A1; GAPDH; HPLC; LC–MS; Prostate; RXR; VDR; Vitamin D receptor; Vitamin D(3); bovine pituitary extract; glyceraldehyde-3-phosphate dehydrogenase; high performance liquid chromatography; liquid chromatography mass spectroscopy; retinoid X receptor; siRNA; small interfering RNA; vitamin D receptor