α-生育酚琥珀酸酯通过线粒体诱导肿瘤细胞凋亡的研究

Study on the effect of α-tocopheryl succinate in inducing apoptosis of tumor cells via mitochondria

α-生育酚琥珀酸酯(α-tocopheryl succinate,α-TOS)是一种有潜力的细胞凋亡诱导剂,可以诱导人类以及小鼠多种肿瘤细胞凋亡。α-TOS进入细胞后,特异性进入线粒体内,替代结合在线粒体内膜复合体Ⅱ上的辅酶Q,引起线粒体活性氧(re-active oxygen species,ROS)的产生,随后由ROS促使细胞质中的凋亡相关蛋白Bax形成由二硫键连接的二聚体,这些二聚体结合到线粒体的外膜(mitochondrial outer membrane,MOM)上,形成通道,促使线粒体内的细胞色素C(cytochrome C,Cyt C)从这些通道穿过,转位到细胞质中,级联激活位于细胞质中的caspase,引起细胞凋亡。本文就α-TOS诱导肿瘤细胞凋亡的线粒体途径进行综述。

α-Tocopheryl succinate（α-TOS） is a potent cell apoptosis inducer and selectively induces apoptosis in many types of cancer cells including human and marine tumor cell lines.Briefly,after α-TOS is uptaken by cancer cells,it specially targets the mitochondrial Complex Ⅱ and displaces ubiquinone from its binding sites in Complex Ⅱ and then causes accumulation of reactive oxygen species（ROS）.ROS promotes dimerization of Bax and causes Bax to translocate to the mitochondrial outer membrane（MOM） to form the channels.The Bax channels on the MOM allow the apoptosis mediators,such as cytochrome C（Cyt C）,to be released from mitochondria to cytoplasm thereby activating intracellular caspases and causing apoptosis.Here we summarized the studies on the mitochondrial pathway in α-TOS-induced apoptosis of tumor cells.