Journal
LEUKEMIA RESEARCH
Volume 30, Issue 8, Pages 1005-1011Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.leukres.2005.12.008
Keywords
ritonavir; 1,25-dihydroxyvitamin D-3; 25-hydroxyvitamin D-3-24-hydroxylase (CYP24); myeloid leukemia; differentiation
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HIV-1 protease inhibitor, ritonavir (RTV) is a potent inhibitor of cytochrome p450 (CYPs) enzymes. This study explored the effects of RTV on CYP24 which converts 1,25-dihydroxyvitamin D-3 [1,25(OH)(2)D-3] to its inactive form 1,24,25,(OH)(3). Real-time RT-PCR showed that exposure of HL-60 cells to 1,25(OH)(2)D-3 induced expression of CYP24, and pre-incubation of these cells with RTV decreased this transcripts, resulting in increased intracellular levels of 1,25(OH)(2)D-3 and potentiation of the ability of 1,25(OH)(2)D-3 to induce growth arrest and differentiation of these cells. Taken together, inhibition of CYP24 might open a new paradigm for therapy using Vitamin D compounds. (c) 2005 Elsevier Ltd. All rights reserved.
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