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
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
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DOI：
10.1016/j.leukres.2005.12.008
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发表时间：
2006-08-01
影响因子：
2.7
通讯作者：
Taguchi, Hirokuni
中科院分区：
文献类型：
--
作者：
Ikezoe, Takayuki;Bandobashi, Kentaro;Taguchi, Hirokuni
HIV-1 蛋白酶抑制剂利托那韦 (RTV) 是细胞色素 p450 (CYP) 酶的有效抑制剂。本研究探讨了 RTV 对 CYP24 的影响，CYP24 将 1,25-二羟基维生素 D-3 [1,25(OH)(2)D-3] 转化为其非活性形式 1,24,25,(OH)(3)。实时 RT-PCR 显示，HL-60 细胞暴露于 1,25(OH)(2)D-3 会诱导 CYP24 表达，而这些细胞与 RTV 预孵育会减少该转录本，导致细胞内 1,25(OH)(2)D-3 水平增加，并增强 1,25(OH)(2)D-3 诱导这些细胞生长停滞和分化的能力。总而言之，抑制 CYP24 可能会为维生素 D 化合物的治疗开辟新的范例。 (c) 2005 Elsevier Ltd. 保留所有权利。
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.