Epigallocatechin-3-gallate enhances ER stress-induced cancer cell apoptosis by directly targeting PARP16 activity.
Epigallocatechin-3-gallate enhances ER stress-induced cancer cell apoptosis by directly targeting PARP16 activity.
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Epigallocatechin-3-gallate 通过直接靶向 PARP16 活性来增强 ER 应激诱导的癌细胞凋亡。
DOI：
10.1038/cddiscovery.2017.34
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发表时间：
2017
影响因子：
7
通讯作者：
Wu J
中科院分区：
文献类型：
--
作者：
Wang J;Zhu C;Song D;Xia R;Yu W;Dang Y;Fei Y;Yu L;Wu J
聚ADP核糖聚合酶（Poly（ADP-ribose）polymerases，PARP）是一种ADP核糖基化酶，在多种细胞过程中发挥重要作用。迄今为止开发的大多数小分子PARP抑制剂都是针对PARP 1（一种聚ADP核糖转移酶）的，并且选择性较差。PARP 16是一种单ADP核糖转移酶，最近已成为一种潜在的治疗靶点，但其抑制剂的开发却落后于人。在这里，我们新的特点表没食子儿茶素-3-没食子酸酯（EGCG）作为PARP 16的潜在抑制剂。我们发现EGCG与PARP 16相关，并在体外显着抑制其活性。此外，EGCG抑制ER应激诱导的PERK磷酸化和未折叠蛋白反应相关基因的转录，导致ER应激条件下的癌细胞凋亡显著增加，这依赖于PARP 16。这些新发现将EGCG作为PARP 16的潜在抑制剂，其可以增强ER应激诱导的癌细胞凋亡，这表明EGCG和ER应激诱导剂的组合可能代表癌症治疗或化学预防的新方法。
Poly(ADP-ribose) polymerases (PARPs) are ADP-ribosylating enzymes and play important roles in a variety of cellular processes. Most small-molecule PARP inhibitors developed to date have been against PARP1, a poly-ADP-ribose transferase, and suffer from poor selectivity. PARP16, a mono-ADP-ribose transferase, has recently emerged as a potential therapeutic target, but its inhibitor development has trailed behind. Here we newly characterized epigallocatechin-3-gallate (EGCG) as a potential inhibitor of PARP16. We found that EGCG was associated with PARP16 and dramatically inhibited its activity in vitro. Moreover, EGCG suppressed the ER stress-induced phosphorylation of PERK and the transcription of unfolded protein response-related genes, leading to dramatically increase of cancer cells apoptosis under ER stress conditions, which was dependent on PARP16. These findings newly characterized EGCG as a potential inhibitor of PARP16, which can enhance the ER stress-induced cancer cell apoptosis, suggesting that a combination of EGCG and ER stress-induced agents might represent a novel approach for cancer therapy or chemoprevention.
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影响因子：
7.4
作者：
Fei, Y. Y.;Schmidt, A.;Bylund, G.;Johansson, D. X.;Henriksson, S.;Lebrilla, C.;Solnick, J. V.;Boren, T.;Zhu, X. D.
通讯作者：
Zhu, X. D.
影响因子：
13.5
作者：
Huang, Weixue;Ding, Liya;Yu, Long
通讯作者：
Yu, Long
影响因子：
1.6
作者：
Fei, Y. Y.;Landry, J. P.;Lam, K. S.
通讯作者：
Lam, K. S.
影响因子：
8
作者：
Luo, B.;Lee, A. S.
通讯作者：
Lee, A. S.
影响因子：
2.1
作者：
Garg AD;Maes H;van Vliet AR;Agostinis P
通讯作者：
Agostinis P