Institute of Environmental Medicine, Division of Toxicology, Karolinska Institutet, Box 210, Stockholm, SE-171 77 Sweden.
Mitochondrion. 2013 Sep;13(5):533-8. doi: 10.1016/j.mito.2012.08.001. Epub 2012 Aug 18.
Targeting mitochondria is a promising strategy in tumor cell elimination. d-α-tocopheryl succinate (α-TOS), a redox-silent analog of vitamin E, is a potentially powerful tool for fighting tumors by directly affecting mitochondria. However, when used at low concentrations it can suppress apoptosis induced by the conventionally used anticancer drug cisplatin. In cells treated with cisplatin, 30μM α-TOS prominently attenuated the manifestation of characteristic features of apoptosis - release of cytochrome c from mitochondria, caspase-3-like activity, and cleavage of poly(ADP-ribose) polymerase. In contrast, cell death induced by etoposide was not inhibited but rather stimulated by α-TOS. Thus, co-treatment with α-TOS and conventional antitumor drugs should be carried out with caution.
靶向线粒体是消除肿瘤细胞的一种很有前途的策略。d-α-生育酚琥珀酸酯(α-TOS)是维生素 E 的一种氧化还原沉默类似物,通过直接作用于线粒体,它可能成为对抗肿瘤的有力工具。然而,当以低浓度使用时,它可以抑制通常使用的抗癌药物顺铂诱导的细胞凋亡。在用顺铂处理的细胞中,30μM 的 α-TOS 明显减弱了凋亡特征的表现 - 线粒体中细胞色素 c 的释放、半胱天冬酶-3 样活性和多聚(ADP-核糖)聚合酶的切割。相比之下,α-TOS 并未抑制依托泊苷诱导的细胞死亡,反而刺激了其发生。因此,α-TOS 与传统抗肿瘤药物联合治疗应谨慎进行。