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题名: Adenanthin targets peroxiredoxin I and II to induce differentiation of leukemic cells
作者: 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; null(孙汉董)4; Chen, Guo-Qiang1, 2, 6
刊名: NATURE CHEMICAL BIOLOGY
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
英文摘要: 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.
出版日期: 2012-05-01
卷号: 8, 期号:5, 页码:486-493
DOI标识: 10.1038/NCHEMBIO.935
语种: 英语
ISSN号: 1552-4450
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.kib.ac.cn/handle/151853/10347
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.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:
Liu, CX; Yin, QQ; Zhou, HC; Wu, YL; Pu, JX; Xia, L; Liu, W; Huang, X; Jiang, T; Wu, MX; He, LC; Zhao, YX; Wang, XL; Xiao, WL; Chen, HZ; Zhao, Q; Zhou, AW; Wang, LS; Sun, HD; Chen, GQ.Adenanthin targets peroxiredoxin I and II to induce differentiation of leukemic cells,NATURE CHEMICAL BIOLOGY,2012,8(5):486-493
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