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    In vitro activity of a G-quadruplex-stabilizing small molecule that synergizes with Navitoclax to induce cytotoxicity in acute myeloid leukemia cells

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    s12885-019-6464-9.pdf
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    Author
    Montoya, Justin J
    Turnidge, Megan A
    Wai, Daniel H
    Patel, Apurvi R
    Lee, David W
    Gokhale, Vijay
    Hurley, Laurence H
    Arceci, Robert J
    Wetmore, Cynthia
    Azorsa, David O
    Affiliation
    Univ Arizona, Coll Med
    Univ Arizona, Coll Pharm
    Issue Date
    2019-12-27
    Keywords
    AML
    Bcl-2
    Bcl-XL
    G-quadruplex
    MYC
    Navitoclax
    
    Metadata
    Show full item record
    Publisher
    BMC
    Citation
    Montoya, J.J., Turnidge, M.A., Wai, D.H. et al. In vitro activity of a G-quadruplex-stabilizing small molecule that synergizes with Navitoclax to induce cytotoxicity in acute myeloid leukemia cells. BMC Cancer 19, 1251 (2019). https://doi.org/10.1186/s12885-019-6464-9
    Journal
    BMC CANCER
    Rights
    Copyright © The Author(s). 2019 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
    Collection Information
    This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at repository@u.library.arizona.edu.
    Abstract
    GQC-05 treatment of KG-1a, CMK and TF-1 cells decreased cell viability and resulted in increased DNA damage and apoptosis. Additionally, treatment of KG-1a, CMK and TF-1 with GQC-05 resulted in decreased expression of MYC mRNA and protein, with a more pronounced effect in KG-1a cells. Combination drug screening identified the Bcl-2/Bcl-XL inhibitor Navitoclax as a compound that potentiated GQC-05 activity. Co-treatment with GQC-05 and Navitoclax showed a synergistic decrease in cell viability of AML cells as determined by Chou-Talalay analysis, and induced more DNA damage, apoptosis, and rapid cytotoxicity. The cytotoxicity induced by GQC-05 and Navitoclax was more potent than that of Navitoclax combined with either cytarabine or doxorubicin.
    Note
    Open access journal
    ISSN
    1471-2407
    PubMed ID
    31881855
    DOI
    10.1186/s12885-019-6464-9
    Version
    Final published version
    Sponsors
    Sharon D. Lund Foundation; University of Arizona COM-P Department of Child Health Mission Support; Phoenix Children's Hospital Foundation; St. Baldrick's Foundation; [5RO1CA177585]
    ae974a485f413a2113503eed53cd6c53
    10.1186/s12885-019-6464-9
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    UA Faculty Publications

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