Antioxidants potentiate American ginseng-induced killing of colorectal cancer cells.
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.
Li
Binghui
B
Ben May Department for Cancer Research, The University of Chicago, Chicago, IL 60637, United States.
Wang
Chong-Zhi
CZ
He
Tong-Chuan
TC
Yuan
Chun-Su
CS
Du
Wei
W
D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D045744:Cell Line, Tumor; D002851:Chromatography, High Pressure Liquid; D015179:Colorectal Neoplasms; D006801:Humans; D008954:Models, Biological; D005894:Panax; D010936:Plant Extracts / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism
D000975:Antioxidants; D010936:Plant Extracts; D017382:Reactive Oxygen Species