Abstract
Colorectal cancer is the third leading cause of cancer-related deaths in the United States. Novel prevention or therapeutic agents are needed to better manage this disease. American ginseng is a commonly used herb and is believed to have lots of health benefits, including anti-cancer activities. However there have been very few in-depth studies of the activities of this herb at the molecular level. In this report we showed that 4h-steamed American ginseng root extract (S4h) induced mitochondrial damage, increased reactive oxygen species (ROS), and apoptosis in colorectal cancer cells. We showed that the NF-kappaB pathway was activated by S4h and that removal of ROS inhibited S4h-induced NF-kappaB activation. We further showed that both antioxidants and a specific inhibitor of the NF-kappaB pathway enhanced S4h-induced cell death. Finally, we showed that protecting the mitochondria decreased both the level of ROS and apoptosis. Taken together, these results indicate that S4h-induced apoptosis in colorectal cancer cells is mediated by mitochondria damage and that damage to the mitochondria activates both the apoptosis pathway and the ROS/NF-kappaB mediated survival pathway. These results further suggest that the anti-cancer effect of steamed ginseng can be enhanced by antioxidants or inhibitors of the NF-kappaB pathway.