Abstract
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.
- Received June 26, 2006.
- Accepted September 12, 2006.
- The American Society for Pharmacology and Experimental Therapeutics
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