A diterpenoid derivate compound targets selenocysteine of thioredoxin reductases and induces Bax/Bak-independent apoptosis
Liu, Jinhua1; Mu, Chenglong1; Yue, Wen2; Li, Jie1; Ma, Biao1; Zhao, Lixia2; Liu, Lei2; Chen, Quan1,2; Yan, Chen3; Liu, Haiyang3; Hao, Xiaojiang3; Zhu, Yushan1
2013-10-01
发表期刊FREE RADICAL BIOLOGY AND MEDICINE
ISSN0891-5849
卷号63期号:SI页码:485-494
摘要We have previously shown that the natural diterpenoid derivative S3 induced Bim upregulation and apoptosis in a Bax/Bak-independent manner. However, the exact molecular target(s) of S3 and the mechanism controlling Bim upregulation are still not clear. Here, we identify that S3 targets the selenoproteins TrxR1 and TrxR2 at the selenocysteine residue of the reactive center of the enzymes and inhibits their antioxidant activities. Consequently, cellular ROS is elevated, leading to the activation of FOXO3a, which contributes to Bim upregulation in Bax/Bak-deficient cells. Moreover, S3 retards tumor growth in subcutaneous xenograft tumors by inhibiting TrxR activity in vivo. Our studies delineate the signaling pathway controlling Bim upregulation, which results in Bax/Bak-independent apoptosis and provide evidence that the compounds can act as anticancer agents based on mammalian TrxRs inhibition. Crown Copyright (C) 2013 Published by Elsevier Inc. All rights reserved.
关键词Thioredoxin Reductase Bim Ros Apoptosis Cancer
资助信息Ministry of Science and Technology of China [2010CB912204, 2011CB910903, 2013CB531200]; National Natural Science Foundation of China [31271529, 91213304, U1032603]
收录类别SCI
语种英语
引用统计
文献类型期刊论文
条目标识符http://ir.kib.ac.cn/handle/151853/16657
专题植物化学与西部植物资源持续利用国家重点实验室
作者单位1.Nankai Univ, Coll Life Sci, Tianjin Key Lab Prot Sci, Tianjin 300071, Peoples R China
2.Chinese Acad Sci, Inst Zool, State Key Lab Biomembrane & Membrane Biotechnol, Beijing 100101, Peoples R China
3.Chinese Acad Sci, Kunming Inst Bot, State Key Lab Phytochem & Plant Resources West Ch, Kunming 650204, Peoples R China
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Liu, Jinhua,Mu, Chenglong,Yue, Wen,et al. A diterpenoid derivate compound targets selenocysteine of thioredoxin reductases and induces Bax/Bak-independent apoptosis[J]. FREE RADICAL BIOLOGY AND MEDICINE,2013,63(SI):485-494.
APA Liu, Jinhua.,Mu, Chenglong.,Yue, Wen.,Li, Jie.,Ma, Biao.,...&Zhu, Yushan.(2013).A diterpenoid derivate compound targets selenocysteine of thioredoxin reductases and induces Bax/Bak-independent apoptosis.FREE RADICAL BIOLOGY AND MEDICINE,63(SI),485-494.
MLA Liu, Jinhua,et al."A diterpenoid derivate compound targets selenocysteine of thioredoxin reductases and induces Bax/Bak-independent apoptosis".FREE RADICAL BIOLOGY AND MEDICINE 63.SI(2013):485-494.
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