HIV-1 protease inhibitor ritonavir potentiates the effect of 1,25-dihydroxyvitamin D3 to induce growth arrest and differentiation of human myeloid leukemia cells via down-regulation of CYP24.
Leuk Res
; 30(8): 1005-11, 2006 Aug.
Article
em En
| MEDLINE
| ID: mdl-16457885
ABSTRACT
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.
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Base de dados:
MEDLINE
Assunto principal:
Esteroide Hidroxilases
/
Calcitriol
/
Leucemia Mieloide
/
Ritonavir
Limite:
Humans
Idioma:
En
Revista:
Leuk Res
Ano de publicação:
2006
Tipo de documento:
Article
País de afiliação:
Japão