Potentiation of reactive oxygen species is a marker for synergistic cytotoxicity of MS-275 and 5-azacytidine in leukemic cells
Potentiation of reactive oxygen species is a marker for synergistic cytotoxicity of MS-275 and 5-azacytidine in leukemic cells
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DOI：
10.1016/j.leukres.2007.09.007
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发表时间：
2008-05-01
影响因子：
2.7
通讯作者：
Chandra, Joya
中科院分区：
文献类型：
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作者：
Gao, Shan;Mobley, Aaron;Chandra, Joya
表观遗传修饰物目前在临床上用于各种类型的肿瘤。最近，大量研究支持组蛋白脱乙酰酶抑制剂(HDACi)和DNA甲基转移酶抑制剂的组合，鼓励这些药物一起进行早期临床试验。在这里，我们显示，MS-275，一种HDACi，和5-氮胞苷，一种甲基转移酶抑制剂，在AML和ALL细胞中显示出协同的细胞毒性和凋亡。在所有细胞中，细胞内产生的活性氧物种(ROS)，如超氧化物和过氧化氢，是这种协同作用的新标志。这些数据表明，氧化应激评估可以作为MS-275和5-氮胞苷协同作用的标志。(C)2007爱思唯尔有限公司。保留所有权利。
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.