Centro de Estudio para las Investigaciones y Evaluaciones Biológicas, Instituto de Farmacia y Alimentos, Universidad de La Habana, La Lisa, Ciudad Habana, Cuba.
Mitochondrion. 2011 Mar;11(2):255-63. doi: 10.1016/j.mito.2010.10.008. Epub 2010 Oct 31.
Nemorosone, a natural-occurring polycyclic polyprenylated acylphloroglucinol, has received increasing attention due to its strong in vitro anti-cancer action. Here, we have demonstrated the toxic effect of nemorosone (1-25 μM) on HepG2 cells by means of the MTT assay, as well as early mitochondrial membrane potential dissipation and ATP depletion in this cancer cell line. In mitochondria isolated from rat liver, nemorosone (50-500 nM) displayed a protonophoric uncoupling activity, showing potency comparable to the classic protonophore, carbonyl cyanide m-chlorophenyl hydrazone (CCCP). Nemorosone enhanced the succinate-supported state 4 respiration rate, dissipated mitochondrial membrane potential, released Ca(2+) from Ca(2+)-loaded mitochondria, decreased Ca(2+) uptake and depleted ATP. The protonophoric property of nemorosone was attested by the induction of mitochondrial swelling in hyposmotic K(+)-acetate medium in the presence of valinomycin. In addition, uncoupling concentrations of nemorosone in the presence of Ca(2+) plus ruthenium red induced the mitochondrial permeability transition process. Therefore, nemorosone is a new potent protonophoric mitochondrial uncoupler and this property is potentially involved in its toxicity on cancer cells.
新木姜子素，一种天然存在的多环多聚异戊烯基酰基间苯三酚，由于其强大的体外抗癌作用而受到越来越多的关注。在这里，我们通过 MTT 测定法证明了新木姜子素（1-25 μM）对 HepG2 细胞的毒性作用，以及这种癌细胞系中线粒体膜电位早期耗散和 ATP 耗竭。在大鼠肝线粒体中，新木姜子素（50-500 nM）表现出质子载体解偶联活性，其效力可与经典的质子载体羰基氰化物 m-氯苯腙（CCCP）相媲美。新木姜子素增强了琥珀酸支持的状态 4 呼吸速率，耗散了线粒体膜电位，从 Ca(2+)-加载的线粒体中释放 Ca(2+)，减少 Ca(2+)摄取并耗尽 ATP。新木姜子素的质子载体特性通过在缬氨霉素存在下在低渗 K(+)-乙酸盐介质中诱导线粒体肿胀得到证明。此外，在 Ca(2+)加钌红存在下的新木姜子素解偶联浓度诱导了线粒体通透性转换过程。因此，新木姜子素是一种新型有效的质子载体线粒体解偶联剂，这种特性可能与其对癌细胞的毒性有关。
