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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Record Fields
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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