PT - JOURNAL ARTICLE AU - Young-Mi Ham AU - Jin-Hee Lim AU - Hye-Kyung Na AU - Joon-Seok Choi AU - Byoung-Duck Park AU - Hyungshin Yim AU - Seung-Ki Lee TI - Ginsenoside-Rh2-Induced Mitochondrial Depolarization and Apoptosis Are Associated with Reactive Oxygen Species- and Ca<sup>2+</sup>-Mediated c-Jun NH<sub>2</sub>-Terminal Kinase 1 Activation in HeLa Cells AID - 10.1124/jpet.106.109926 DP - 2006 Dec 01 TA - Journal of Pharmacology and Experimental Therapeutics PG - 1276--1285 VI - 319 IP - 3 4099 - http://jpet.aspetjournals.org/content/319/3/1276.short 4100 - http://jpet.aspetjournals.org/content/319/3/1276.full SO - J Pharmacol Exp Ther2006 Dec 01; 319 AB - We show here that Ca2+ and reactive oxygen species (ROS) are involved in the up-regulation of c-Jun NH2-terminal kinase 1 (JNK1) activity during apoptosis induced by ginsenoside Rh2 (G-Rh2) in HeLa, MCF10A-ras, and MCF7 cells. Addition of antioxidants such as N-acetyl-l-cysteine or catalase attenuates G-Rh2-induced ROS generation, JNK1 activation, and apoptosis. The overexpression of catalase down-regulates caspase-3 and JNK1 activities. G-Rh2 treatment of cells results in mitochondrial depolarization, second mitochondrial activator of caspase release, and translocation of Bax into the mitochondria, and these events are inhibited by antioxidants. Ca2+ is also involved in mitochondrial depolarization during G-Rh2-induced apoptosis. These results suggest that ROS and Ca2+ are important signaling intermediates leading to stress-activated protein kinase/extracellular signal-regulated kinase kinase 1/JNK1 activation and depolarization of the mitochondrial membrane potential in G-Rh2-induced apoptosis.