Ginsenoside Rh2 induces apoptosis and paraptosis-like cell death in colorectal cancer cells through activation of p53.
Ginsenoside Rh2 induces apoptosis and paraptosis-like cell death in colorectal cancer cells through activation of p53.
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DOI：
10.1016/j.canlet.2010.11.015
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发表时间：
2011-02-28
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;Zhao, Jiong;Wang, Chong-Zhi;Searle, Jennifer;He, Tong-Chuan;Yuan, Chun-Su;Du, Wei
人参皂苷是西洋参的主要生物活性成分，是一种常用的草药。在本研究中，我们发现人参皂苷Rh2在HCT116和SW480结直肠癌细胞中表现出比人参皂苷Rg3更强的细胞死亡活性。Rh2诱导的细胞死亡部分由caspase依赖性凋亡介导，部分由caspase非依赖性凋亡介导，这是一种以细胞质空泡积累为特征的细胞死亡类型。用Rh2处理细胞激活p53通路，显著增加促凋亡调节因子Bax的水平，同时降低抗凋亡调节因子Bcl-2的水平。去除p53可显著阻断Rh2诱导的细胞死亡和液泡形成，提示Rh2诱导的两种细胞死亡均由p53活性介导。此外，我们发现Rh2增加ROS水平并激活NF-κB存活途径。NAC或过氧化氢酶阻断ROS可抑制NF-κB信号的激活，增强Rh2诱导的细胞死亡，提示抗氧化剂可增强Rh2的抗癌作用。
Ginsenosides are the main bioactive components in American ginseng, a commonly used herb. In this study, we showed that the ginsenoside Rh2 exhibited significantly more potent cell death activity than the ginsenoside Rg3 in HCT116 and SW480 colorectal cancer cells. Cell death induced by Rh2 is mediated in part by the caspase-dependent apoptosis and in part by the caspase-independent paraptosis, a type of cell death that is characterized by the accumulation of cytoplasmic vacuoles. Treatment of cells with Rh2 activated the p53 pathway and significantly increased the levels of the pro-apoptotic regulator, Bax, while decreasing the levels of anti-apoptosis regulator Bcl-2. Removal of p53 significantly blocked Rh2 induced cell death as well as vacuole formation, suggesting that both types of cell death induced by Rh2 are mediated by p53 activity. Furthermore, we show that Rh2 increased ROS levels and activated the NF-κB survival pathway. Blockage of ROS by NAC or catalase inhibited the activation of NF-κB signaling and enhanced Rh2-induced cell death, suggesting that the anticancer effect of Rh2 can be enhanced by antioxidants.
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