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

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

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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

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.

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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

Collections

UA Faculty Publications