The Role of CCAAT/Enhancer Binding Protein (C/EBP) Homologous Protein (CHOP) in the Antileukemic Activity of Artemisinins
AdvisorCivin, Curt I.
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AbstractCurrent 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.
DescriptionUniversity of Maryland, Baltimore. Medical Biochemistry. M.S. 2022.
Transcription Factor CHOP
Leukemia, Myeloid, Acute