Adenanthin targets peroxiredoxin I and II to induce differentiation of leukemic cells
Liu, Chuan-Xu1; Yin, Qian-Qian2; Zhou, Hu-Chen3; Wu, Ying-Li1; Pu, Jian-Xin4; Xia, Li1; Liu, Wei1; Huang, Xin2; Jiang, Tao5; Wu, Ming-Xuan3; He, Li-Cai1; Zhao, Ya-Xue3; Wang, Xiao-Lin5; Xiao, Wei-Lie4; Chen, Hong-Zhuan5; Zhao, Qian1; Zhou, Ai-Wu1; Wang, Li-Shun1; Sun, Han-Dong4; Chen, Guo-Qiang1,2,6
Corresponding AuthorLiu, CX (reprint author), Shanghai Jiao Tong Univ, Sch Med, Shanghai Univ E Inst Chem Biol,Chinese Minist Edu, Dept Pathophysiol,Key Lab Cell Differentiat Apopt, Shanghai 200030, Peoples R China, chengq@shsmu.edu.cn
2012-05-01
Source PublicationNATURE CHEMICAL BIOLOGY
ISSN1552-4450
Volume8Issue:5Pages:486-493
Abstract

Peroxiredoxins (Prxs) are potential therapeutic targets for major diseases such as cancers. However, isotype-specific inhibitors remain to be developed. We report that adenanthin, a diterpenoid isolated from the leaves of Rabdosia adenantha, induces differentiation of acute promyelocytic leukemia (APL) cells. We show that adenanthin directly targets the conserved resolving cysteines of Prx I and Prx II and inhibits their peroxidase activities. Consequently, cellular H2O2 is elevated, leading to the activation of extracellular signal-regulated kinases and increased transcription of CCAAT/enhancer-binding protein beta, which contributes to adenanthin-induced differentiation. Adenanthin induces APL-like cell differentiation, represses tumor growth in vivo and prolongs the survival of mouse APL models that are sensitive and resistant to retinoic acid. Thus, adenanthin can serve as what is to our knowledge the first lead natural compound for the development of Prx I-and Prx II-targeted therapeutic agents, which may represent a promising approach to inducing differentiation of APL cells.

KeywordCimicifuga Foetida Cycloartane Cytotoxicity Ranunculaceae Breast-cancer Cells Crude Drug Shoma Racemosa Extract Simplex Wormsk Cyclolanostanol Xylosides Triterpene Glycosides Chemical-constituents Prostate-cancer Aerial Parts Black Cohosh
Subject AreaBiochemistry & Molecular Biology
DOI10.1038/NCHEMBIO.935
Indexed BySCI
Language英语
WOS Research AreaBiochemistry & Molecular Biology
WOS SubjectBiochemistry & Molecular Biology
WOS IDWOS:000302962500016
Citation statistics
Cited Times:96[WOS]   [WOS Record]     [Related Records in WOS]
Document Type期刊论文
Identifierhttp://ir.kib.ac.cn/handle/151853/10347
Collection植物化学与西部植物资源持续利用国家重点实验室
Affiliation1.Shanghai Jiao Tong Univ, Sch Med, Shanghai Univ E Inst Chem Biol,Chinese Minist Edu, Dept Pathophysiol,Key Lab Cell Differentiat Apopt, Shanghai 200030, Peoples R China
2.Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Hlth Sci, Shanghai, Peoples R China
3.Shanghai Jiao Tong Univ, Sch Pharm, Shanghai 200030, Peoples R China
4.Chinese Acad Sci, Kunming Inst Bot, State Key Lab Phytochem & Plant Resources W China, Kunming, Yunnan, Peoples R China
5.Shanghai Jiao Tong Univ, Sch Med, Dept Pharmacol, Shanghai 200030, Peoples R China
6.Shanghai Jiao Tong Univ, Sch Med, State Key Lab Oncogenes & Related Genes, Shanghai Canc Inst,Ren Ji Hosp, Shanghai 200030, Peoples R China
Recommended Citation
GB/T 7714
Liu, Chuan-Xu,Yin, Qian-Qian,Zhou, Hu-Chen,et al. Adenanthin targets peroxiredoxin I and II to induce differentiation of leukemic cells[J]. NATURE CHEMICAL BIOLOGY,2012,8(5):486-493.
APA Liu, Chuan-Xu.,Yin, Qian-Qian.,Zhou, Hu-Chen.,Wu, Ying-Li.,Pu, Jian-Xin.,...&Chen, Guo-Qiang.(2012).Adenanthin targets peroxiredoxin I and II to induce differentiation of leukemic cells.NATURE CHEMICAL BIOLOGY,8(5),486-493.
MLA Liu, Chuan-Xu,et al."Adenanthin targets peroxiredoxin I and II to induce differentiation of leukemic cells".NATURE CHEMICAL BIOLOGY 8.5(2012):486-493.
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