Antioxidants potentiate American ginseng-induced killing of colorectal cancer cells.
Antioxidants potentiate American ginseng-induced killing of colorectal cancer cells.
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DOI：
10.1016/j.canlet.2009.08.002
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发表时间：
2010-03-01
期刊：
影响因子：
9.7
通讯作者：
Du, Wei
中科院分区：
文献类型：
--
作者：
Li, Binghui;Wang, Chong-Zhi;He, Tong-Chuan;Yuan, Chun-Su;Du, Wei
结直肠癌是美国癌症相关死亡的第三大原因。需要新的预防或治疗药物来更好地管理这种疾病。西洋参是一种常用的草药，被认为有很多健康益处，包括抗癌活性。然而，在分子水平上对这种草药的活性进行深入研究的很少。在这份报告中，我们表明，4小时蒸西洋参根提取物（S4 h）诱导线粒体损伤，增加活性氧（ROS），并在结直肠癌细胞凋亡。我们发现NF-κB通路被S4 h激活，清除ROS抑制了S4 h诱导的NF-κB激活。我们进一步表明，抗氧化剂和NF-κB通路的特异性抑制剂都能增强S4 h诱导的细胞死亡。最后，我们发现保护线粒体降低了ROS水平和细胞凋亡。总之，这些结果表明，S4 h诱导的结直肠癌细胞凋亡是由线粒体损伤介导的，线粒体损伤激活了凋亡途径和ROS/NF-κB介导的存活途径。这些结果进一步表明，抗氧化剂或NF-κB通路抑制剂可以增强蒸人参的抗癌作用。
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 anticancer 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 4 hour-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-κB pathway was activated by S4h and that removal of ROS inhibited S4h-induced NF-κB activation. We further showed that both antioxidants and a specific inhibitor of the NF-κB 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-κB mediated survival pathway. These results further suggest that the anticancer effect of steamed ginseng can be enhanced by antioxidants or inhibitors of the NF-κB pathway.
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