二氯醋酸钠激活C6细胞线粒体代谢途径的体外作用

doi:10.5246/jcps.2011.05.058

二氯醋酸钠激活C6细胞线粒体代谢途径的体外作用

赵欣, 王欣, 余克富, 段瑀, 李捷思, 赵炳祥, 张烜^*, 张强

1. 北京大学医学部药学院药剂学系, 100191 北京
2. 北京大学医学部天然药物及仿生药物国家重点实验室, 100191 北京

收稿日期:2011-05-16 修回日期:2011-07-25 出版日期:2011-09-20 发布日期:2011-09-20
通讯作者: 张烜*

Effects of dichloroacetate on the activation of the mitochondrial pathway in C6 cells in vitro

Xin Zhao, Xin Wang, Ke-Fu Yu, Yu Duan, Jie-Si Li, Bing-Xiang Zhao, Xuan Zhang^*, Qiang Zhang

1. Department of Pharmaceutics, School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing 100191, China
2. State Key Laboratory of Natural and Biomimetic Drugs, Peking University Health Science Center, Beijing 100191, China

Received:2011-05-16 Revised:2011-07-25 Online:2011-09-20 Published:2011-09-20
Contact: Xuan Zhang*

摘要/Abstract

摘要：

肿瘤细胞线粒体代谢途径已成为抗肿瘤的关注点。二氯醋酸钠 (DCA)是作用于线粒体的小分子物质, 显示出一定的抗肿瘤作用。因此, 本文考察DCA对C6脑胶质瘤细胞线粒体代谢途径的影响。实验结果显示, DCA可显著增加C6细胞丙酮酸脱氢酶 (PDH)的活性、诱导C6细胞氧活性物质 (ROS)的生成, 显著降低C6细胞线粒体膜电位 (MMP)。上述结果表明, DCA可通过激活C6细胞线粒体代谢途径产生抗肿瘤作用。线粒体代谢途径将成为抗肿瘤治疗的新靶点。

关键词: 线粒体代谢, 二氯醋酸钠, C6脑胶质瘤细胞, 丙酮酸脱氢酶, 氧活性物质, 线粒体膜电位

Abstract: Mitochondria are increasingly recognized as important targets for tumor treatment because of their central roles in apoptotic pathways and cellular metabolism. Dichloroacetate (DCA), a low molecular weight mitochondria-targeting agent, exhibits potential therapeutic effects for tumors. Based on the effects of DCA on tumor cellular metabolism, we carried out this study to investigate the anti-tumor activity of DCA in C6 glioma cells in vitro. The results showed that DCA was able to increase the activity of pyruvate dehydrogenase (PDH), induce the production of reactive oxygen species (ROS) and reduce the mitochondrial membrane potential (MMP) in C6 cells in vitro (P<0.05 or 0.01), indicating that the anti-tumor effects of DCA in C6 cells could be through the activation of the mitochondrial pathway. In conclusion, mitochondria could be a viable therapeutic target for the treatment of glioma.

Key words: Mitochondria metabolism, Dichloroacetate, C6 glioma, Pyruvate dehydrogenase, Reactive oxygen species, Mitochondrial membrane potential

中图分类号:

R962

Supporting:

Foundation items: National Natural Science Foundation of China (Grant No. 30873170) and the National Basic Research Program of China (973 Program 2007CB935800 and 2009CB930300).
^*Corresponding author. Tel./Fax: 86-10-82802683

赵欣, 王欣, 余克富, 段瑀, 李捷思, 赵炳祥, 张烜^*, 张强. 二氯醋酸钠激活C6细胞线粒体代谢途径的体外作用[J]. , DOI: 10.5246/jcps.2011.05.058.

Xin Zhao, Xin Wang, Ke-Fu Yu, Yu Duan, Jie-Si Li, Bing-Xiang Zhao, Xuan Zhang^*, Qiang Zhang. Effects of dichloroacetate on the activation of the mitochondrial pathway in C6 cells in vitro [J]. , DOI: 10.5246/jcps.2011.05.058.

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