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表没食子儿茶素-3-没食子酸酯使人类786-O肾癌细胞对肿瘤坏死因子相关凋亡诱导配体(TRAIL)诱导的凋亡敏感。

Epigallocatechin-3-gallate Sensitizes Human 786-O Renal Cell Carcinoma Cells to TRAIL-Induced Apoptosis.

作者信息

Wei Ruojing, Zhu Guodong, Jia Ning, Yang Wenzeng

机构信息

The Affiliated Hospital of Hebei University, Baoding, China.

The First Affiliated Hospital of Xian Jiaotong University, Xi'an, China.

出版信息

Cell Biochem Biophys. 2015 May;72(1):157-64. doi: 10.1007/s12013-014-0428-0.

Abstract

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a promising anticancer agent. Epigallocatechin-3-gallate (EGCG) is a polyphenolic constituent of green tea. In this study, potentiating effect of EGCG on TRAIL-induced apoptosis human renal carcinoma cell line 786-O which is relatively resistant to TRAIL was examined, and the possible mechanism was investigated. Here, we show that co-treatment with EGCG and TRAIL induced significantly more profound apoptosis in 786-O cells. Treatment of 786-O cells with EGCG and TRAIL downregulated c-FLIP, Mcl-1, and Bcl-2 proteins in a caspase-dependent pathway. Moreover, we found that pretreatment with NAC markedly inhibited the expression levels of c-FLIP, Mcl-1, and Bcl-2 downregulated by the combinatory treatment, suggesting that the regulating effect of EGCG on these above apoptosis-relevant molecules was partially mediated by generation of ROS. Taken together, the present study demonstrates that EGCG sensitizes human 786-O renal cell carcinoma cells to TRAIL-induced apoptosis by downregulation of c-FLIP, Mcl-1, and Bcl-2.

摘要

肿瘤坏死因子相关凋亡诱导配体(TRAIL)是一种很有前景的抗癌药物。表没食子儿茶素-3-没食子酸酯(EGCG)是绿茶中的一种多酚成分。在本研究中,检测了EGCG对相对抵抗TRAIL的人肾癌细胞系786-O中TRAIL诱导凋亡的增强作用,并研究了其可能的机制。在此,我们表明EGCG与TRAIL联合处理在786-O细胞中诱导了更显著的凋亡。用EGCG和TRAIL处理786-O细胞通过半胱天冬酶依赖性途径下调了c-FLIP、Mcl-1和Bcl-2蛋白。此外,我们发现用NAC预处理显著抑制了联合处理下调的c-FLIP、Mcl-1和Bcl-2的表达水平,表明EGCG对上述凋亡相关分子的调节作用部分是由活性氧的产生介导的。综上所述,本研究表明EGCG通过下调c-FLIP、Mcl-1和Bcl-2使人类786-O肾癌细胞对TRAIL诱导的凋亡敏感。

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