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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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

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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/). 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]
Collections
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/). 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.
Except where otherwise noted, this item's license is described as 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/). 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.