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
2012-05-01
发表期刊NATURE CHEMICAL BIOLOGY
ISSN1552-4450
卷号8期号:5页码:486-493
摘要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.
关键词Cimicifuga 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
资助信息National Basic Research Program of China[NO2009CB918404]; National Natural Science Foundation of China (NSFC)[90813034, 81070433]; Shanghai Science and Technology Commission[11IC1406800, 11JC1406500]; NSFC joint Foundation of Yunnan Province[U0832602]; Shanghai Committee of Education
学科领域Biochemistry & Molecular Biology
DOI10.1038/NCHEMBIO.935
收录类别SCI
语种英语
WOS研究方向Biochemistry & Molecular Biology
WOS类目Biochemistry & Molecular Biology
WOS记录号WOS:000302962500016
引用统计
被引频次:84[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.kib.ac.cn/handle/151853/10347
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.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
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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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