ReferenceID 499

Adenanthin targets peroxiredoxin I and II to induce differentiation of leukemic cells

Nat Chem Biol

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 o

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Reference Id
499
Evidence Id
17089
Core Evidence Id
17089
Source Reference Id
975
Herb2 Reference Id
HBREF001686
Subject Paper Key
HBIN014672_22484541
Pubmed Id
22484541
Doi
10.1038/nchembio.935
Paper Title
Adenanthin targets peroxiredoxin I and II to induce differentiation of leukemic cells
Paper 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 H(2)O(2) is elevated, leading to the activation of extracellular signal-regulated kinases and increased transcription of CCAAT/enhancer-binding protein β, 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.
Journal
Nat Chem Biol
Publish Year
2012
Experiment Subject
apl cell
Experiment Type
Cell Experiment
Phenotype Related
Acute Promyelocytic Leukemia
Paper Title Cn
Paper Title En
Adenanthin targets peroxiredoxin I and II to induce differentiation of leukemic cells
Bilingual Status
semi_complete