Possible role of glutathione in mitochondrial apoptosis of human oral squamous cell carcinoma caused by inorganic selenium compounds.
Possible role of glutathione in mitochondrial apoptosis of human oral squamous cell carcinoma caused by inorganic selenium compounds.
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DOI：
10.3892/ijo.27.2.489
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发表时间：
2005-08
影响因子：
5.2
通讯作者：
Masato Takahashi;Tomonori Sato;F. Shinohara;S. Echigo;H. Rikiishi
中科院分区：
文献类型：
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作者：
Masato Takahashi;Tomonori Sato;F. Shinohara;S. Echigo;H. Rikiishi
硒是一种非常有效的抗癌剂。我们研究了无机硒化合物诱导细胞凋亡的作用，通过硒化合物发挥化学预防癌症的活性。以HSC-3人口腔鳞状细胞癌细胞为研究对象，本研究表明，Se以SeO_2和Na_2SeO_3的形式作用72 h，而不以Na_2SeO_4的形式处理72 h，可明显诱导细胞凋亡，且呈剂量依赖关系。100微米SeO2处理HSC-3细胞后，Caspase-3和-9样活化。Se化合物引起线粒体膜电位(DeltaPsim)的丧失，但不诱导活性氧的产生。经SeO2处理18h后，与Se代谢有关的还原型谷胱甘肽(GSH)损失了80%。N-乙酰-L-半胱氨酸或外源性谷胱甘肽可阻止SeO2诱导的细胞凋亡。GSH可部分逆转SeO2诱导的DeltaPsim降低，而丁硫氨酸亚磺胺可增强SeO2或Na2SeO_3诱导的细胞凋亡。这些结果表明，Se对线粒体氧化还原平衡的调节参与了线粒体途径，在不增加ROS的情况下调节caspase-9介导的细胞凋亡。
Selenium (Se) is a very effective anti-cancer agent. We studied the effects of inorganic Se compounds on induction of apoptosis by which Se compounds exert cancer chemopreventive activity. With the use of HSC-3 human oral squamous cell carcinoma cells, the present study showed that treatment with Se for 72 h, in the form of SeO2 and Na2SeO3, but not Na2SeO4, markedly induced apoptosis in a dose-dependent manner. Treatment of HSC-3 cells with 100 microM SeO2 resulted in the caspase-3-like and -9-like activation. Se compounds induced a loss of mitochondrial membrane potential (DeltaPsim), but did not induce the generation of reactive oxygen species. Treatment with SeO2 for 18 h resulted in 80% loss of reduced glutathione (GSH), which is known to be involved in the metabolism of Se. Treatment with N-acetyl-L-cysteine, or exogenous GSH, prevented the SeO2-induced apoptosis. Treatment with GSH led to the partial reverse in reduction of DeltaPsim caused by SeO2, while buthionine sulfoximine augmented the SeO2- or Na2SeO3-induced apoptosis. These results suggest that modulation of the mitochondrial redox equilibrium by Se contributes to the mitochondrial pathway, regulating caspase-9-mediated apoptosis without a concurrent increase in ROS.