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; Kawamura, Masaki; Ikushiro, Shinichi; Sakaki, Toshiyuki

doi:10.1016/j.mce.2013.11.014

Cited by 44 publications

(48 citation statements)

References 37 publications

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“…Consistent with these findings, we also observed the antiproliferative effects of 25(OH)D 3 and 1α,25 (OH) 2 D 3 in prostate cells (Munetsuna et al, 2014). In addition, we found that proliferation of PZ-HPV-7 cells was inhibited by 25(OH)-19-nor-D 3 (Munetsuna et al, 2011;Fig.…”

Section: The Antiproliferative Effect Of 25(oh)-19-nor-d 3 In the Humsupporting

confidence: 89%

“…Our recent studies on the metabolism of 25(OH)D 3 in PZ-HPV-7 cells demonstrated that a very low level of 1α,25(OH) 2 D 3 is produced in the cells (Munetsuna et al, 2014). In the presence of 10 or 100 nM 25(OH)D 3 in the culture medium, only 0.016 and 0.15 nM of 1α,25(OH) 2 D 3 was detected, respectively.…”

Section: Cellular Metabolism Of 25(oh)-19-nor-dmentioning

confidence: 95%

“…Thus, VDR translocation into the nucleus has been accepted as an indicator of the biological activities of vitamin D and its analogs. Although VDR is found in both cytoplasm and nucleus under normal conditions, 1α,25(OH) 2 D 3 treatment can cause VDR tranlocation into the nucleus (Munetsuna et al, 2014).…”

Section: The Translocation Of Vdr Into the Nucleusmentioning

confidence: 99%

“…The authors therefore hypothesized that vitamin D deficiency could be a risk factor for prostate cancer. Thereafter, many studies have demonstrated the antiproliferative activity of 1α,25(OH) 2 D 3 in prostate cells derived from either normal or cancerous prostate tissues Feldman, Krishnan, Swami, Giovannucci, & Feldman, 2014;Flanagan et al, 2009;Iglesias-Gato et al, 2011;Munetsuna et al, 2014). Furthermore, animal studies using xenograft models indicated an antitumor effects of dietary vitamin D 3 (Ray et al, 2012) and 1α,25(OH) 2 D 3 (Blutt, Polek, Stewart, Kattan, & Weigel, 2000).…”

Section: Introductionmentioning

confidence: 99%

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Metabolism and Action of 25-Hydroxy-19-nor-Vitamin D3 in Human Prostate Cells

et al. 2016

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Section: The Antiproliferative Effect Of 25(oh)-19-nor-d 3 In the Humsupporting

confidence: 89%

Section: Cellular Metabolism Of 25(oh)-19-nor-dmentioning

confidence: 95%

Section: The Translocation Of Vdr Into the Nucleusmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Metabolism and Action of 25-Hydroxy-19-nor-Vitamin D3 in Human Prostate Cells

et al. 2016

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“…25(OH)VD3 is an active hormone without being converted into 1α,25-(OH)2VD3 in various types of cells [9, 10, 31]. The distinct roles of 25(OH)VD3 and 1α,25-(OH)2VD3 had also been illuminated.…”

Section: Discussionmentioning

confidence: 99%

An in vitro Experimental Insight into the Osteoblast Responses to Vitamin D3 and Its Metabolites

Wang

Song

2018

Pharmacology

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Background: 25-hydroxyvitamin D3 (25[OH]VD3) has recently been found to be an active hormone. Its biological actions are also demonstrated in various cell types. However, the precise influences of vitamin D3 (VD3) and its metabolites (25[OH]VD3, 1α,25-dihydroxyvitamin D3 [1α,25-(OH)2VD3]) on the osteoblast differentiation remain largely unknown. In this work, we investigated the effects of VD3 and its metabolites in different concentrations on the early and later osteoblast differentiation and biomineralization. Methods: We first used quantitative real-time polymerase chain reaction (RT-qPCR) to evaluate the responsiveness of osteoblasts to VD3, 25(OH)VD3 or 1α,25-(OH)2VD3. We also evaluated the proliferation, differentiation and biomineralization of osteoblast at different time points via cell counting kit-8 assay and the analysis of osteogenic markers. Results: The experimental results confirmed that osteoblasts could be responsive to 25(OH)VD3 and 1α,25-(OH)2VD3 but could not directly metabolize VD3 and 25(OH)VD3. Only 200 nmol/L VD3 significantly promoted osteoblast proliferation, while 25(OH)VD3 and 1α,25-(OH)2VD3 did not show obvious actions. Moreover, the early osteogenic markers were increased by 25(OH)VD3 and 1α,25-(OH)2VD3 in a dose-dependent manner. More importantly, only 25(OH)VD3 had accelerated the gene and protein expressions of osteocalcin and the biomineralization level of osteoblasts. Conclusions: Our findings provide reliable evidence that 25(OH)VD3 at 100–200 nmol/L can induce the early and later osteoblast differentiation and biomineralization for clinical bone tissue engineering.

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Human hepatic metabolism of the anti‐osteoporosis drug eldecalcitol involves sterol C4‐methyl oxidase

Yasuda

Iwanaga

Ogawa

et al. 2015

Pharmacology Res & Perspec

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The metabolism of eldecalcitol (ED-71), a 2β-hydroxypropoxylated analog of the active form of vitamin D3 was investigated by using in vitro systems. ED-71 was metabolized to 1α,2β,25-trihydroxyvitamin D3 (1α,2β,25(OH)3D3) in human small intestine and liver microsomes. To identify the enzymes involved in this metabolism, we examined NADPH-dependent metabolism by recombinant P450 isoforms belonging to the CYP1, 2, and 3 families, and revealed that CYP3A4 had the activity. However, the CYP3A4 -specific inhibitor, ketoconazole, decreased the activity in human liver microsomes by only 36%, suggesting that other enzymes could be involved in ED-71 metabolism. Because metabolism was dramatically inhibited by cyanide, we assumed that sterol C4-methyl oxidase like gene product (SC4MOL) might contribute to the metabolism of ED-71. It is noted that SC4MOL is physiologically essential for cholesterol synthesis. Recombinant human SC4MOL expressed in COS7, Saccharomyces cerevisiae, or Escherichia coli cells converted ED-71 to 1α,2β,25(OH)3D3. Furthermore, we evaluated the metabolism of ED-71 by recombinant CYP24A1, which plays an important role in the metabolism of the active form of vitamin D3 (1α,25(OH)2D3) and its analogs. The kcat/Km value for 24- or 23-hydroxylation of ED-71 was only 3% of that for 1α,25(OH)2D3, indicating that ED-71 was resistant to CYP24A1-dependent catabolism. Among the three enzymes catalyzing ED-71, SC4MOL appears to be most important in the metabolism of ED-71. To the best of our knowledge, this is the first study showing that SC4MOL can function as a drug-metabolizing enzyme. The yeast and E. coli expression systems for SC4MOL could be useful for structure-function analyses of SC4MOL.

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

Cited by 44 publications

References 37 publications

Metabolism and Action of 25-Hydroxy-19-nor-Vitamin D3 in Human Prostate Cells

Metabolism and Action of 25-Hydroxy-19-nor-Vitamin D3 in Human Prostate Cells

An in vitro Experimental Insight into the Osteoblast Responses to Vitamin D3 and Its Metabolites

Human hepatic metabolism of the anti‐osteoporosis drug eldecalcitol involves sterol C4‐methyl oxidase

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