Dicoumarol Alters Cellular Redox State and Inhibits Nuclear Factor Kappa B to Enhance Arsenic Trioxide-Induced Apoptosis
Dicoumarol Alters Cellular Redox State and Inhibits Nuclear Factor Kappa B to Enhance Arsenic Trioxide-Induced Apoptosis作者机构：Department of Cell Biology Shanghai Second Medical University Shanghai 200025 China
出 版 物：《Acta Biochimica et Biophysica Sinica》 (生物化学与生物物理学报(英文版))
年 卷 期：2004年第36卷第3期
页 面：235-242页
核心收录：
学科分类：0710[理学-生物学] 07[理学] 071009[理学-细胞生物学] 09[农学] 0901[农学-作物学] 090102[农学-作物遗传育种]
主 题：dicoumarol arsenic trioxide reduction/ oxidation state apoptosis NF-κB
摘 要：The effects of a number of cytotoxic drugs are influenced by cellular reduction/oxidation (redox) state. In the present study, we attempt to explore if dicoumarol, an inhibitor of NADPH: quinone oxidoreductase (NQO1), alters the cellular redox state and how this alteration affects the redox-related apoptosis. Flow cytometry was used to assess the reactive oxygen species (ROS) level and apoptotic rates of HeLa cells treated with arsenic trioxide (As2O3) alone or in combination with natural anthraquinone emodin and dicoumarol or plus N-acetyl-cysteine. Western blot, immunofluorescence, electrophoretic mobility shift assay and luciferase assay were used to detect Nuclear Factor kappa B (NF-κB) activation. The results showed that dicoumarol synergized with emodin to sensitize HeLa cells to As2O3-induced apoptosis through raising the ROS level. More notably, this enhanced susceptibility was associated with a ROS-mediated inhi- bition of NF-κB activation in which the combinative treatment with dicoumarol prevented NF-κB from binding to target DNA. It was suggested that dicoumarol in combination with anthraquinones might be a novel strategy to expand the chemotherapeutic spectrum of As2O3 by means of interfering the cellular redox state.
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