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Participation of vitamin D-upregulated protein 1 (TXNIP)-ASK1-JNK1 signalosome in the enhancement of AML cell death by a post-cytotoxic differentiation regimen

The Journal of Steroid Biochemistry and Molecular Biology(2019)

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摘要
•A vitamin D2 analog (D2) combined with a plant-derived antioxidant carnosic acid (CA) can potentiate the therapeutic effect of AraC on AML blasts.•D2/CA activates apoptotic signals in cells with DNA damage resulting from AraC treatment.•Vitamin D-upregulated protein TXNIP is a regulator of the apoptotic cascade triggered by the differentiation agents (D2/CA) in this system.•TXNIP targets the apoptosis signal regulating kinase ASK1, which then sequentially activates MKK4 and JNK and the executioners of apoptosis.•These data may provide a paradigm for future improvements of Cytarabine-based therapy of patients with AML.
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关键词
AML,AraC,CA,CD,ECD,D2,OD
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