Differential biological effects of 1,25-dihydroxyVitamin D3 on melanoma cell lines in vitro

Seifert, Markus; Rech, Martin; Meineke, Viktor; Tilgen, Wolfgang; Reichrath, Jörg

doi:10.1016/j.jsbmb.2004.03.002

Cited by 69 publications

(90 citation statements)

References 21 publications

(22 reference statements)

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“…We examined the effect of calcitriol on cell proliferation in nine human glioblastoma multiforme cell lines and rat glioblastoma multiforme cell line C6. Melanoma cell line MeWo, known as sensitive for calcitriol (24), served as control. We confirmed a growth inhibition of 56.3 F 8.8% in the latter cell line by 10 À7 mol/L calcitriol.…”

Section: Resultsmentioning

confidence: 99%

Vitamin D3 Metabolism in Human Glioblastoma Multiforme: Functionality of CYP27B1 Splice Variants, Metabolism of Calcidiol, and Effect of Calcitriol

Diesel

Radermacher

Bureik

et al. 2005

Clinical Cancer Research

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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, 1a,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. HighperformanceTLC was done to determine the endogenous CYP27B1activity and the functionality of CYP27B1splice variants. Using WST-1assay, 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 CYP27B1in 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 CYP27B1and CYP24 but left the expression of theVDR 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^r elated therapies.The classic metabolism of the secosteroid hormone vitamin D 3 to its active form followed by several degradation pathways is well described. Vitamin Besides renal CYP27B1 activity, extrarenal CYP27B1 expression has been described in a variety of tissues (4). In vitro, several nonrenal cells, including microglial cells (5), produce calcitriol from its precursor. In addition, several cancer cells show CYP27B1 activity (e.g., human non -small cell lung carcinoma cells; ref. 6). Local production of calcitriol has been postulated to play an autocrine or paracrine role in vitamin Dmediated growth control (7).As shown for numerous normal and cancer cell lines, calcitriol is at high concentrations (10 À9 to 10 À6 mol/L) an antiproliferative and prodifferentiating agent that induces apoptosis and inhibits cell migration (8). The antiproliferative properties of calcitriol, as described above, were also shown for central nervous system tumors, including glioblastoma cell lines (9). Beneficial effects of the vitamin D 3 metabolite 1a-hydroxyvitamin D 3 have been reported for the treatment of glioblastoma multiforme in a small phase II clinical study (10).

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Section: Resultsmentioning

confidence: 99%

Vitamin D3 Metabolism in Human Glioblastoma Multiforme: Functionality of CYP27B1 Splice Variants, Metabolism of Calcidiol, and Effect of Calcitriol

Diesel

Radermacher

Bureik

et al. 2005

Clinical Cancer Research

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“…We studied effects of 1,25-dihydroxyvitamin D 3 [1,25(OH) 2 Vitamin D receptor (VDR) and respond to the antiproliferative activity of 1,25(OH) 2 D 3 . 4 Since these first observations, it has been convincingly shown that 1,25(OH) 2 D 3 and analogs inhibit proliferation and induce differentiation and apoptosis in various malignancies, including human malignant melanoma.…”

Section: Introductionmentioning

confidence: 99%

“…4 Since these first observations, it has been convincingly shown that 1,25(OH) 2 D 3 and analogs inhibit proliferation and induce differentiation and apoptosis in various malignancies, including human malignant melanoma. [1][2][3][4][5] However, tumor cell lines that fail to respond to the antiproliferative effects of vitamin D analogs have also been reported. It is well known that 1,25(OH) 2 D 3 acts via binding to a corresponding intranuclear receptor (VDR), present in target tissues.…”

Section: Introductionmentioning

confidence: 99%

In vitro comparison of the vitamin D endocrine system in 1,25(OH)2D3-responsive and –Resistant melanoma cells

Reichrath

Rech²,

Moeini³

et al. 2007

Cancer Biology & Therapy

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“…Quantitative real-time, reverse transcription polymerase chain reaction (RT-PCR) analysis techniques were used to characterize the activity of the genes associated with vitamin D metabolism: CYP24A1, CYP27A1, CYP27B1 and VDR [16,29]. In addition, RT-PCR was used to detect levels of osteopontin (OP), procollagen type I (proColI) and osteocal- In the second week of culture, the BMP+ EtOH control had a larger amount of calcium deposition in comparison with the treatment groups (P < 0.05).…”

Section: Gene Sequencingmentioning

confidence: 99%

“…VDR belongs to the nuclear hormone receptor family and serves as a ligand-dependent transcription factor (TF) that controls the expression of vitamin D associated target genes which include those associated with calcium homeostasis, cellular proliferation and differentiation, cell division and cycle arrest, and apoptosis [15][16][17][18][19]. Upon 1,25OH2D3 binding, VDR forms a heterodimer with the retinoid X receptor, which allows it to bind to vitamin D receptor elements (VDREs) in the promoter regions of target genes [8,14,17,20].…”

Section: Introductionmentioning

confidence: 99%

The Influence of Vitamin D Metabolism on Gene Expression, Matrix Production and Mineralization During Osteoprecursor Cell-Based Bone Development

et al. 2014

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Background: Multipotential precursor cell lines derived from human bone marrow, capable of differentiating into cartilage or bone, may provide a useful tissue development model for studying the regulation and metabolism of putative growth and differentiation factors necessary for tissue regeneration. In mammals, the process of bone development depends on the proliferation and differentiation of osteoblast lineage cells, and the subsequent synthesis and mineralization of bone extracellular matrix (ECM). Vitamin D metabolites play a pivotal role in bone and mineral homeostasis, and are positive factors on bone development. Recently, it was demonstrated that a human-derived engineered osteoblast precursor cell line (OPC1), derived from human bone marrow, can metabolize the parental precursor vitamin D 3 (vitaD 3 ) to the active steroid 1α,25-dihydroxyvitamin D 3 (1,25OH 2 D 3 ), and elicit an osteogenic response that results in the decrease in proliferation and increase in ECM synthesis during early bone development. The aim in this study is to characterize gene expression, matrix production and mineralization within a bone development model.

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Differential biological effects of 1,25-dihydroxyVitamin D3 on melanoma cell lines in vitro

Cited by 69 publications

References 21 publications

Vitamin D3 Metabolism in Human Glioblastoma Multiforme: Functionality of CYP27B1 Splice Variants, Metabolism of Calcidiol, and Effect of Calcitriol

Vitamin D3 Metabolism in Human Glioblastoma Multiforme: Functionality of CYP27B1 Splice Variants, Metabolism of Calcidiol, and Effect of Calcitriol

In vitro comparison of the vitamin D endocrine system in 1,25(OH)2D3-responsive and –Resistant melanoma cells

The Influence of Vitamin D Metabolism on Gene Expression, Matrix Production and Mineralization During Osteoprecursor Cell-Based Bone Development

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