Vitamin D(3) metabolism in human glioblastoma multiforme: functionality of CYP27B1 splice variants, metabolism of calcidiol, and effect of calcitriol.

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Diesel B, Radermacher J, Bureik M, Bernhardt R, Seifert M, Reichrath J, Fischer U, Meese E

Vitamin D(3) metabolism in human glioblastoma multiforme: functionality of CYP27B1 splice variants, metabolism of calcidiol, and effect of calcitriol.

Clin Cancer Res. 2005 Aug 1;11(15):5370-80.

PubMed ID

16061850 [ View in PubMed

]

Abstract

PURPOSE: A better understanding of the vitamin D(3) metabolism is required to evaluate its potential therapeutic value for cancers. Here, we set out to contribute to the understanding of vitamin D(3) metabolism in glioblastoma multiforme. EXPERIMENTAL DESIGN: We did nested touchdown reverse transcription-PCR (RT-PCR) to identify CYP27B1 splice variants and real-time RT-PCR to quantify the expression of CYP27B1. A cell line was treated with calcitriol to determine the effect on the expression of CYP27B1, 1alpha,25-dihydroxyvitamin D(3)-24-hydroxylase (CYP24), and vitamin D(3) receptor (VDR). We generated three antibodies for the specific detection of CYP27B1 and splice variants. High-performance TLC was done to determine the endogenous CYP27B1 activity and the functionality of CYP27B1 splice variants. Using WST-1 assay, we determined the effect of vitamin D(3) metabolites on proliferation. RESULTS: We report a total of 16 splice variants of CYP27B1 in glioblastoma multiforme and a different expression of CYP27B1 and variants between glioblastoma multiforme and normal tissues. We found preliminary evidence for enzymatic activity of endogenous CYP27B1 in glioblastoma multiforme cell cultures but not for the functionality of the splice variants. By adding calcitriol, we found a proliferative effect for some cell lines depending on the dose of calcitriol. The administration of calcitriol led to an elevated expression of CYP27B1 and CYP24 but left the expression of the VDR unaltered. CONCLUSIONS: Our findings show that glioblastoma multiforme cell lines metabolize calcidiol. In addition, we show various effects mediated by calcitriol. We found a special vitamin D(3) metabolism and mode of action in glioblastoma multiforme that has to be taken into account in future vitamin D(3)-related therapies.

DrugBank Data that Cites this Article

Drug Enzymes

Drug	Enzyme	Kind	Organism	Pharmacological Action	Actions
Calcifediol	25-hydroxyvitamin D-1 alpha hydroxylase, mitochondrial	Protein	Humans	Unknown	Substrate	Details

Pharmaco-transcriptomics

Drug	Drug Groups	Gene	Gene ID	Change	Interaction	Chromosome
Calcitriol	Approved Nutraceutical	CYP24A1	1591	upregulated	Calcitriol results in increased expression of CYP24A1 mRNA	20q13.2
Calcitriol	Approved Nutraceutical	CYP27B1	1594	upregulated	Calcitriol results in increased expression of CYP27B1 mRNA	12q14.1