Role of thioredoxin in the response of normal and transformed cells to histone deacetylase inhibitors
作者： J. S. Ungerstedt , Y. Sowa , W.-S. Xu , Y. Shao , M. Dokmanovic
关键词: Biology 、 Cell culture 、 Cancer cell 、 Transfection 、 Apoptosis 、 Caspase 、 Programmed cell death 、 Cell biology 、 Thioredoxin 、 Histone deacetylase inhibitor
摘要: This study examines the basis of resistance and sensitivity normal transformed cells to histone deacetylase inhibitor (HDACi)-induced cell death, specifically role caspases thioredoxin (Trx). An important attribute HDACis is that they induce cancer death at concentrations which are relatively resistant, making them well suited for therapy. The mechanism underlying this selectivity has not been understood. In we found HDACi suberoylanilide hydroxamic acid (SAHA) MS-275, a benzamide, cause an accumulation reactive oxygen species (ROS) caspase activation in but cells. Inhibition does block HDACi-induced death. These studies provide possible can explain why certain resistant causes increase level Trx, major reducing protein many targets, SAHA-induced Trx activity associated with no ROS accumulation. Transfection small interfering RNA caused marked decrease ROS, proliferation, Thus, independent apoptotic pathway, determinant
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