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

被引：16

作者：

Ikezoe, Takayuki

Bandobashi, Kentaro

Yang, Yang

Takeuchi, Eisho

Sekiguchi, Nobuo

Sakai, Shuichi

Koeffler, H. Phillip

Taguchi, Hirokuni

机构：

[1] Kochi Univ, KMS, Dept Hematol & Resp Dis, Nankoku, Kochi 7838505, Japan

[2] Chugai Pharmaceut Co Ltd, Fuji Gotemba Res Labs, Shizuoka 4128513, Japan

[3] Univ Calif Los Angeles, Cedars Sinai Med Ctr, Sch Med, Los Angeles, CA 90048 USA

来源：

LEUKEMIA RESEARCH | 2006年 / 30卷 / 08期

基金：

美国国家卫生研究院;

关键词：

ritonavir; 1,25-dihydroxyvitamin D-3; 25-hydroxyvitamin D-3-24-hydroxylase (CYP24); myeloid leukemia; differentiation;

D O I：

10.1016/j.leukres.2005.12.008

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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.

引用

页码：1005 / 1011

页数：7

共 29 条

[1] 19-nor vitamin-D analogs: A new class of potent inhibitors of proliferation and inducers of differentiation of human myeloid leukemia cell lines [J].