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Au nanoclusters suppress chronic lymphocytic leukaemia cells by inhibiting thioredoxin reductase 1 to induce intracellular oxidative stress and apoptosis

文献类型:期刊论文

作者Zhao, M; Gao, L; Liu, R; Wang, YL; Gong, Y; Gao, FP; Gao, XY; Gong Y(龚勇); Li, Q; Yuan, Q
刊名SCIENCE BULLETIN科学通报
出版日期2017
卷号62期号:8页码:537-545
关键词Chronic lymphocytic leukaemia (CLL) Gold nanoclusters Thioredoxin reductase (TrxR) Mitochondrial membrane potential (MMP) Apoptosis
ISSN号2095-9273
DOI10.1016/j.scib.2017.03.024
文献子类Article
英文摘要Chronic lymphocytic leukaemia (CLL) is a rare blood cancer that always relapses as refractory disease and eventually leads to death. To date, therapeutic options for CLL patients are scarce and there is an urgent need to develop novel chemotherapeutics that are both effective and safe. Gold-containing compounds induce a lethal oxidative and endoplasmic reticulum stress response in cultured and primary CLL cells via inhibition of thioredoxin reductase (TrxR). However, traditional gold-containing medicines have revealed side effects during clinical applications. Therefore, safer gold-containing drugs are needed to overcome this challenge. In this study, a novel peptide templated gold cluster Au25Sv9 was synthesized and its therapeutic effect on CLL cells was evaluated. This nanocluster could induce cell apoptosis in MEC-1 cells in a dose-dependent manner which correlated with the uptake amount of clusters in cells. As expected, increasing intracellular reactive oxidative species (ROS) in MEC-1 cells was exhibited with the increase of cluster dosage. Further analyses demonstrated the underlying mechanism that the nanoclusters suppress the activity of TrxR1, increase the level of intracellular ROS, destroy the mitochondrial membrane potential and finally trigger the mitochondrial apoptotic pathway in MEC-1 cells. Furthermore, the direct interaction between Au25Sv9 clusters and TrxR1 was confirmed for the first time by isothermal titration calorimetry. These findings explored the preclinical efficacy and potential mechanism of gold clusters in CLL therapy and provided a fundamental reference for the development of other novel gold-containing chemotherapeutics to treat CLL. (C) 2017 Science China Press. Published by Elsevier B.V. and Science China Press. All rights reserved.
电子版国际标准刊号2095-9281
WOS关键词BIOMEDICAL APPLICATIONS ; RHEUMATOID-ARTHRITIS ; CYTOTOXIC SECRETIONS ; AURANOFIN ; GOLD ; DRUG ; MECHANISM ; CANCER ; TUMOR ; TRXR1
WOS研究方向Science & Technology - Other Topics
语种英语
CSCD记录号CSCD:6006884
WOS记录号WOS:000403561400003
源URL[http://ir.ihep.ac.cn/handle/311005/285220]  
专题高能物理研究所_多学科研究中心
高能物理研究所_实验物理中心
高能物理研究所_粒子天体物理中心
高能物理研究所_管理与技术支持
作者单位中国科学院高能物理研究所
推荐引用方式
GB/T 7714
Zhao, M,Gao, L,Liu, R,et al. Au nanoclusters suppress chronic lymphocytic leukaemia cells by inhibiting thioredoxin reductase 1 to induce intracellular oxidative stress and apoptosis[J]. SCIENCE BULLETIN科学通报,2017,62(8):537-545.
APA Zhao, M.,Gao, L.,Liu, R.,Wang, YL.,Gong, Y.,...&Yao, YW.(2017).Au nanoclusters suppress chronic lymphocytic leukaemia cells by inhibiting thioredoxin reductase 1 to induce intracellular oxidative stress and apoptosis.SCIENCE BULLETIN科学通报,62(8),537-545.
MLA Zhao, M,et al."Au nanoclusters suppress chronic lymphocytic leukaemia cells by inhibiting thioredoxin reductase 1 to induce intracellular oxidative stress and apoptosis".SCIENCE BULLETIN科学通报 62.8(2017):537-545.

入库方式: OAI收割

来源:高能物理研究所

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