Simons, Claire  ORCID: https://orcid.org/0000-0002-9487-1100, Yee, S. W. and Campbell, M. J.
2006.
Inhibition of vitamin D3 metabolism enhances VDR signalling in androgen-independent prostate cancer cells.
The Journal of Steroid Biochemistry and Molecular Biology
98
(4-5)
, pp. 228-235.
10.1016/j.jsbmb.2005.11.004
|
Abstract
Induction of growth arrest and differentiation by 1α,25-dihydroxyvitamin D3 (1,25-(OH)2D3) occurs in non-malignant cell types but is often reduced in cancer cells. For example, androgen-independent prostate cancer cells, DU-145 and PC-3, are relatively insensitive to the anti-proliferative action of 1,25-(OH)2D3. This appears to be due to increased 1,25-(OH)2D3-metabolism, as a result of CYP24 enzyme-induction, which in turn leads to decreased anti-proliferative efficacy. In the in vitro rat kidney mitochondria assay, the 2-(4-hydroxybenzyl)-6-methoxy-3,4-dihydro-2H-naphthalen-1-one (4) was found to be a potent inhibitor of Vitamin D3 metabolising enzymes (IC50 3.5 μM), and was shown to be a more potent inhibitor than the broad spectrum P450 inhibitor ketoconazole (IC50 20 μM). The combination of the inhibitor and 1,25-(OH)2D3 caused a greater inhibition of proliferation in DU-145 cells than when treated with both agents alone. Examination of the regulation of VDR target gene mRNA in DU-145 cells revealed that co-treatment of 1,25-(OH)2D3 plus inhibitor of Vitamin D3 metabolising enzymes co-ordinately upregulated CYP24, p21waf1/cip1 and GADD45α.
| Item Type: | Article |
|---|---|
| Date Type: | Publication |
| Status: | Published |
| Schools: | Schools > Pharmacy |
| Subjects: | R Medicine > RS Pharmacy and materia medica |
| Uncontrolled Keywords: | Vitamin D3 metabolising enzymes; Tetralone; Prostate cancer cells |
| Publisher: | Elsevier |
| ISSN: | 0960-0760 |
| Last Modified: | 17 Oct 2022 08:45 |
| URI: | https://orca.cardiff.ac.uk/id/eprint/950 |
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