Enhancement of arabinocytosine (AraC) toxicity to AML cells by a differentiation agent combination

The Journal of Steroid Biochemistry and Molecular Biology
Xuening WangG P Studzinski

Abstract

Arabinocytosine (AraC, also known as cytarabine) is one of the mainstays of AML therapy, but like other DNA damaging therapeutic agents it is rarely curative by itself. There is an emerging realization that the therapeutic outcomes may be improved by combining AraC with other compounds. Here we report that the addition of a differentiating agent combination immediately following AraC damage to AML blasts, selectively increases the cell kill. The experiments were performed using cultured cells from established cell lines of AML (HL60 and U937). The cells were exposed to 100nM AraC, a concentration which produced approximately 25-50% cell kill, followed by a combination of 100nM 1alpha-hydroxyvitamin D2 (1-D2) and 10μM carnosic acid (CA), which together can serve as a powerful differentiating agent combination for AML cells, but are not toxic alone. AraC-induced cell death, measured by annexin V/propidium iodide, was significantly (p<0.01) increased by the 1-D2/CA combination in both cell lines, but not by 1-D2 or CA alone. The enhancement of cell death occurred by both apoptosis and necrosis, was associated with increased DNA damage and with higher levels of DNA damage response (DDR) activated marker Chk1, but the expression of ...Continue Reading

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Citations

Mar 10, 2016·Data in Brief·Joseph S HarrisonBrian Kuhlman
Mar 6, 2019·Phytotherapy Research : PTR·Yu-Hsin TsengPei-Chin Lin
Nov 23, 2017·Nature Communications·Alessandro Di TullioDominique Bonnet
Dec 22, 2020·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·Ai-Mei LiaoChangJu Chun
Aug 3, 2017·The Journal of Steroid Biochemistry and Molecular Biology·Xuening WangGeorge P Studzinski

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