细胞培养中氨基酸的稳定同位素标记
细胞凋亡
DNA损伤
炎症
生物
氧化应激
蛋白质组学
定量蛋白质组学
细胞生物学
癌症研究
化学
生物化学
免疫学
基因
DNA
作者
Guang‐Rong Yan,Zi-Lu Tan,Yang Wang,Manli Xu,Guangchuang Yu,Yao-Lan Li,Qing‐Yu He
出处
期刊:Proteomics
[Wiley]
日期:2013-08-23
卷期号:13 (21): 3222-3232
被引量:26
标识
DOI:10.1002/pmic.201300152
摘要
Isolated from Elephantopus scaber L., a Chinese medicinal herb that is widely used to prevent and treat cancers in China, isodeoxyelephantopin (ESI) exerted antitumor effects on several cancer cells. However, its antitumor mechanism is still not clear. In this study, we found that ESI could induce G2/M arrest and subsequently stimulate cell apoptosis in dose- and time-dependent manners. We used SILAC quantitative proteomics to identify ESI-regulated proteins in cancer cells, and found that 124 proteins were significantly altered in expression. Gene ontology and Ingenuity Pathway Analysis revealed that these proteins were mainly involved in the regulation of oxidative stress and inflammation response. Functional studies demonstrated that ESI induced G2/M arrest and apoptosis by inducing ROS generation, and that antioxidant N-acetyl-l-cysteine could block the ESI-induced antitumor effects. Accumulated ROS resulted in DNA breakage, subsequent G2/M arrest and mitochondrial-mediated apoptosis. ESI upregulated the expression of anticancer inflammation factors IL-12a, IFN-α, and IFN-β through ROS-dependent and independent pathways. The current work reveals that ESI exerts its antitumor effects through ROS-dependent DNA damage, mitochondrial-mediated apoptosis mechanism and antitumor inflammation factor pathway.
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