Lemeshko Victor V, Haridas Valsala, Quijano Pérez Jairo C, Gutterman Jordan U
Escuela de Física, Facultad de Ciencias, Universidad Nacional de Colombia, sede Medellín, AA3840 Medellín, Colombia.
Arch Biochem Biophys. 2006 Oct 15;454(2):114-22. doi: 10.1016/j.abb.2006.08.008. Epub 2006 Aug 23.
Avicins are a class of natural saponins with selective pro-apoptotic activity in cancer cells. In this work, we studied the influence of avicins on metabolic state of rat liver mitochondria. Avicin-treated mitochondria underwent a significant decrease in oxygen consumption rate that was completely restored by addition of exogenous cytochrome c. On the other hand, avicins increased the rotenone-insensitive oxidation of external NADH in the presence of exogenous cytochrome c, long before high amplitude swelling of mitochondria was observed. The increase in external NADH oxidation was cyclosporin A-insensitive. Avicin G significantly accelerated hydroperoxide-induced oxidation of mitochondrial endogenous NAD(P)H, the drop of the inner membrane potential and the high amplitude swelling of mitochondria. The obtained data might explain selective induction of apoptosis in tumor cells by avicins. Based on other studies showing that tumor cells generate hydroperoxides with a very high rate, avicins could provide a new strategy of anticancer therapy by sensitizing cells with high levels of reactive oxygen species to apoptosis.
阿魏菌素是一类在癌细胞中具有选择性促凋亡活性的天然皂苷。在本研究中，我们研究了阿魏菌素对大鼠肝线粒体代谢状态的影响。用阿魏菌素处理的线粒体耗氧率显著降低，添加外源性细胞色素c后可完全恢复。另一方面，在外源性细胞色素c存在的情况下，早在观察到线粒体高幅度肿胀之前，阿魏菌素就增加了鱼藤酮不敏感的胞外NADH氧化。胞外NADH氧化的增加对环孢素A不敏感。阿魏菌素G显著加速了过氧化氢诱导的线粒体内源性NAD(P)H氧化、内膜电位下降和线粒体高幅度肿胀。所获得的数据可能解释了阿魏菌素对肿瘤细胞凋亡的选择性诱导作用。基于其他研究表明肿瘤细胞以非常高的速率产生过氧化氢，阿魏菌素可能通过使具有高水平活性氧的细胞对凋亡敏感而提供一种新的抗癌治疗策略。
