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    The Role of CCAAT/Enhancer Binding Protein (C/EBP) Homologous Protein (CHOP) in the Antileukemic Activity of Artemisinins

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    Author
    Tabassum, Sumiya
    0000-0002-2086-9737
    Advisor
    Civin, Curt I.
    Date
    2022
    Type
    dissertation
    
    Metadata
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    Abstract
    Current chemotherapy options for acute myeloid leukemia (AML) are still limited, despite recent efforts to develop novel drugs for AML with greater efficacy and acceptable toxicity. Several antimalarial analogs of the compound artemisinin (ARTs) possess antineoplastic activity across many cancer cell types, with highest potency against leukemia cells, but their detailed molecular mechanisms of action (MOA) are inconclusively established. This study leveraged our previous findings that ARTs downregulated the antiapoptotic protein, myeloid cell leukemia-1 (MCL1), and upregulated the transcription factor, CCATT/enhancer-binding protein homologous protein (CHOP), in human AML cells. We assessed the roles of these molecules in the antileukemic MOA of the highly potent ART analog, ART838, in the human MOLM14 AML cell line. We found that enforced MCL1 overexpression rescues from ART838-mediated cell death. However, neither CHOP overexpression nor CRISPR-Cas9-mediated CHOP knockout affected growth/survival or cellular levels of MCL1 protein, in the absence or presence of ART838.
    Description
    University of Maryland, Baltimore. Medical Biochemistry. M.S. 2022.
    Keyword
    ART838
    MCL1
    Transcription Factor CHOP
    CCAAT-Enhancer-Binding Proteins
    Artemisinins
    Leukemia, Myeloid, Acute
    Identifier to cite or link to this item
    http://hdl.handle.net/10713/19238
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