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  • Title: Targeting thioredoxin reductase by deoxyelephantopin from Elephantopus scaber triggers cancer cell apoptosis.
    Author: Duan D, Wang Y, Pan D, Wang L, Xiao J, Song P, Jin X, Wang X.
    Journal: Arch Biochem Biophys; 2021 Oct 30; 711():109028. PubMed ID: 34509463.
    Abstract:
    Elevated expression of thioredoxin reductase (TrxR) is associated with the tumorigenesis and resistance to cancer chemoradiotherapy, highlighting the potential of TrxR inhibitors as anticancer drugs. Deoxyelephantopin (DET) is the major active ingredient of Elephantopus scaber and reveals potent anticancer activity. However, the potential mechanism of action and the cellular target of DET are still unknown. Here, we found that DET primarily targets the Sec residue of TrxR and irreversibly prohibits enzyme activity. Suppression of TrxR by DET leads to accumulation of reactive oxygen species and dysregulation in intracellular redox balance, eventually inducing cancer cell apoptosis mediated by oxidative stress. Noticeably, down-regulation of TrxR1 by shRNA increases cell sensitivity to DET. Collectively, targeting of TrxR1 by DET uncovers a novel mechanism of action in DET and deepens the understanding of developing DET as a potential chemotherapeutic agent for treating cancers.
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