Linked Life Data

17553915

Source:http://linkedlifedata.com/resource/pubmed/id/17553915

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
9
pubmed:dateCreated
2007-8-22
pubmed:abstractText
Our previous study demonstrated that 25-hydroxy-19-nor-vitamin D(3) [25(OH)-19-nor-D(3)] inhibited the proliferation of immortalized noncancerous PZ-HPV-7 prostate cells similar to 1 alpha,25-dihydroxyvitamin D(3) [1 alpha,25(OH)(2)D(3)], suggesting that 25(OH)-19-nor-D(3) might be converted to 1 alpha,25-dihydroxy-19-nor-vitamin D(3) [1 alpha,25(OH)(2)-19-nor-D(3)] by CYP27B1 before exerting its antiproliferative activity. Using an in vitro cell-free model to study the kinetics of CYP27B1-dependent 1 alpha-hydroxylation of 25(OH)-19-nor-D(3) and 25-hydroxyvitamin D(3) [25(OH)D(3)] and CYP24A1-dependent hydroxylation of 1 alpha,25(OH)-19-nor-D(3) and 1 alpha,25(OH)(2)D(3), we found that k(cat)/K(m) for 1 alpha-hydroxylation of 25(OH)-19-nor-D(3) was less than 0.1% of that for 25(OH)D(3), and the k(cat)/K(m) value for 24-hydroxylation was not significantly different between 1 alpha,25(OH)(2)-19-nor-D(3) and 1 alpha,25(OH)(2)D(3). The data suggest a much slower formation and a similar rate of degradation of 1 alpha,25(OH)(2)-19-nor-D(3) compared with 1 alpha,25(OH)(2)D(3). We then analyzed the metabolites of 25(OH)D(3) and 25(OH)-19-nor-D(3) in PZ-HPV-7 cells by high-performance liquid chromatography. We found that a peak that comigrated with 1 alpha,25(OH)(2)D(3) was detected in cells incubated with 25(OH)D(3), whereas no 1 alpha,25(OH)(2)-19-nor-D(3) was detected in cells incubated with 25(OH)-19-nor-D(3). Thus, the present results do not support our previous hypothesis that 25(OH)-19-nor-D(3) is converted to 1 alpha,25(OH)(2)-19-nor-D(3) by CYP27B1 in prostate cells to inhibit cell proliferation. We hypothesize that 25(OH)-19-nor-D(3) by itself may have a novel mechanism to activate vitamin D receptor or it is metabolized in prostate cells to an unknown metabolite with antiproliferative activity without 1 alpha-hydroxylation. Thus, the results suggest that 25(OH)-19-nor-D(3) has potential as an attractive agent for prostate cancer therapy.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0090-9556
pubmed:author
pubmed:issnType
Print
pubmed:volume
35
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1482-8
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:17553915-25-Hydroxyvitamin D3 1-alpha-Hydroxylase, pubmed-meshheading:17553915-Animals, pubmed-meshheading:17553915-Calcitriol, pubmed-meshheading:17553915-Carbon Monoxide, pubmed-meshheading:17553915-Cattle, pubmed-meshheading:17553915-Cell Line, pubmed-meshheading:17553915-Cell Proliferation, pubmed-meshheading:17553915-Cholecalciferol, pubmed-meshheading:17553915-Chromatography, High Pressure Liquid, pubmed-meshheading:17553915-Cytochrome P-450 Enzyme System, pubmed-meshheading:17553915-Escherichia coli, pubmed-meshheading:17553915-Humans, pubmed-meshheading:17553915-Hydroxylation, pubmed-meshheading:17553915-Kinetics, pubmed-meshheading:17553915-Male, pubmed-meshheading:17553915-Models, Molecular, pubmed-meshheading:17553915-Plasmids, pubmed-meshheading:17553915-Prostate, pubmed-meshheading:17553915-Steroid Hydroxylases, pubmed-meshheading:17553915-Thymus Gland
pubmed:year
2007
pubmed:articleTitle
Kinetic studies of 25-hydroxy-19-nor-vitamin D3 and 1 alpha,25-dihydroxy-19-nor-vitamin D3 hydroxylation by CYP27B1 and CYP24A1.
pubmed:affiliation
Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Kitashirakawa, Oiwake-cho, Sakyo-ku, Kyoto, Japan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't