In vitro activity of a G-quadruplex-stabilizing small molecule that synergizes with Navitoclax to induce cytotoxicity in acute myeloid leukemia cells
AuthorMontoya, Justin J
Turnidge, Megan A
Wai, Daniel H
Patel, Apurvi R
Lee, David W
Hurley, Laurence H
Arceci, Robert J
Azorsa, David O
AffiliationUniv Arizona, Coll Med
Univ Arizona, Coll Pharm
MetadataShow full item record
CitationMontoya, 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
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AbstractGQC-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.
NoteOpen access journal
VersionFinal published version
SponsorsSharon D. Lund Foundation; University of Arizona COM-P Department of Child Health Mission Support; Phoenix Children's Hospital Foundation; St. Baldrick's Foundation; [5RO1CA177585]
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