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J Steroid Biochem Mol Biol. 2013 Jul;136:252-7. doi: 10.1016/j.jsbmb.2012.09.031. Epub 2012 Oct 8.

24-Hydroxylase in cancer: impact on vitamin D-based anticancer therapeutics.

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  • 1Department of Pharmacology and Therapeutics, Roswell Park Cancer Institute, Buffalo, NY 14263, United States.

Abstract

The active vitamin D hormone 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) plays a major role in regulating calcium homeostasis and bone mineralization. 1,25(OH)2D3 also modulates cellular proliferation and differentiation in a variety of cell types. 24-Hydroxylase, encoded by the CYP24A1 gene, is the key enzyme which converts 1,25(OH)2D3 to less active calcitroic acid. Nearly all cell types express 24-hydroxylase, the highest activity being observed in the kidney. There is increasing evidence linking the incidence and prognosis of certain cancers to low serum 25(OH)D3 levels and high expression of vitamin D 24-hydroxylase, supporting the idea that elevated CYP24A1 expression may stimulate degradation of vitamin D metabolites including 25(OH)D3 and 1,25(OH)2D3. The over expression of CYP24A1 in cancer cells may be a factor affecting 1,25(OH)2D3 bioavailability and anti-proliferative activity pre-clinically and clinically. The combination of 1,25(OH)2D3 with CYP24A1 inhibitors enhances 1,25(OH)2D3 mediated signaling and anti-proliferative effects and may be useful in overcoming effects of aberrant CYP24A1 expression. This article is part of a Special Issue entitled 'Vitamin D Workshop'.

Copyright © 2012 Elsevier Ltd. All rights reserved.

PMID:
23059474
[PubMed - indexed for MEDLINE]
PMCID:
PMC3686893
Free PMC Article
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