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题名: A diterpenoid derivate compound targets selenocysteine of thioredoxin reductases and induces Bax/Bak-independent apoptosis
作者: Liu, Jinhua1; Mu, Chenglong1; Yue, Wen2; Li, Jie1; Ma, Biao1; Zhao, Lixia2; Liu, Lei2; Chen, Quan1, 2; Yan, Chen3; null(刘海洋)3; null(郝小江)3; Zhu, Yushan1
刊名: FREE RADICAL BIOLOGY AND MEDICINE
关键词: Thioredoxin reductase ; Bim ; ROS ; Apoptosis ; Cancer
英文摘要: 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.
出版日期: 2013-10-01
卷号: 63, 期号:SI, 页码:485-494
语种: 英语
收录类别: SCI
学科分类: Biochemistry & Molecular Biology; Endocrinology & Metabolism
ISSN号: 0891-5849
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.kib.ac.cn/handle/151853/16657
Appears in Collections:植物化学与西部植物资源持续利用国家重点实验室_期刊论文

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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

Recommended Citation:
Liu, Jinhua; Mu, Chenglong; Yue, Wen; Li, Jie; Ma, Biao; Zhao, Lixia; Liu, Lei; Chen, Quan; Yan, Chen; Liu, Haiyang; Hao, Xiaojiang; Zhu, Yushan.A diterpenoid derivate compound targets selenocysteine of thioredoxin reductases and induces Bax/Bak-independent apoptosis,FREE RADICAL BIOLOGY AND MEDICINE,2013,63(SI):485-494
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