Potentiation of reactive oxygen species is a marker for synergistic cytotoxicity of MS-275 and 5-azacytidine in leukemic cells

被引:55
作者
Gao, Shan [1 ]
Mobley, Aaron [1 ]
Miller, Claudia [1 ]
Boklan, Jessica [2 ]
Chandra, Joya [1 ]
机构
[1] Childrens Canc Hosp, MD Anderson Canc Ctr, Dept Pediat Res, Houston, TX 77030 USA
[2] Phoenix Childrens Hosp, Ctr Canc & Blood Disorders, Phoenix, AZ USA
关键词
MS-275; 5-azacytidine; historic deacetylase inhibitor; DNA methyltransferase; reactive oxygen species;
D O I
10.1016/j.leukres.2007.09.007
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Epigenetic modifiers are currently in clinical use for various tumor types. Recently, numerous studies supporting the combination of histone deacetylase inhibitors (HDACi) and DNA methyltransferase inhibitors have emerged, encouraging early clinical trials of these agents together. Here we show that MS-275, an HDACi, and 5-azacytidine, a methyltransferase inhibitor, display synergistic cytotoxicity and apoptosis in AML and ALL cells. Intracellular production of reactive oxygen species (ROS), such as superoxide and hydrogen peroxide, is a novel marker for this synergism in ALL cells. These data suggest that assessment of oxidative stress can serve as a marker of the concerted action of MS-275 and 5-azacytidine. (C) 2007 Elsevier Ltd. All rights reserved.
引用
收藏
页码:771 / 780
页数:10
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