J Steroid Biochem Mol Biol. 2012 Oct 8. pii: S0960-0760(12)00200-2. doi: 10.1016/j.jsbmb.2012.09.031
Luo W, Hershberger PA, Trump DL, Johnson CS.
Department of Pharmacology and Therapeutics.
The active vitamin D hormone 1,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3)) plays a major role in regulating calcium homeostasis and bone mineralization. 1,25(OH)(2)D(3) 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)(2)D(3) 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)D(3) 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)D(3) and 1,25(OH)(2)D(3).
The over expression of CYP24A1 in cancer cells may be a factor affecting 1,25(OH)(2)D(3) bioavailability and anti-proliferative activity pre-clinically and clinically.
The combination of 1,25(OH)(2)D(3) with CYP24A1 inhibitors enhances 1,25(OH)(2)D(3) mediated signaling and anti-proliferative effects and may be useful in overcoming effects of aberrant CYP24 expression.
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