Anti-leukemic effects of the quercetin on human leukemia U937 cells mediated by down-regulation of Mcl-1, survivin, and XIAP

Abstract

Recently, flavonoid quercetin is described as a natural product capable of the treatment of various types of leukemia, such as acute myeloid leukemia (AML), by targeting various survival and proliferation-associated signaling pathways or molecules. Herein, we evaluated the anti-leukemic effects of the quercetin on the human AML cell line, U937. Accordingly, the proliferation rate of the U937 cells was examined using MTT assay at 6, 12, and 24 hours of treatment with a series of quercetin concentrations, including 10, 20, 30, 40, 80, and 120 µM. Moreover, the apoptosis rates of U937 cells were estimated 6, 12, and 24 hours after exposure to quercetin 30 µM using annexin-V/PI staining and fluorescence-activated cell sorting (FACS) analysis. Finally, the expression rates of survivin, Mcl-1, XIAP, Bcl-2, and Bax were measured after treatment with quercetin 20 and 40 µM using Real-Time PCR within 6 and 12 hours of treatment. Concerning results, quercetin induced significant apoptosis in U937 cells within 6, 12, and 24 hours of treatment. Moreover, results verified the inhibitory effect of quercetin on U937 cell proliferation, more powerfully at 24 hours of exposure. Additionally, quercetin robustly modified Mcl-1, XIAP, and survivin expression at mRNA levels without any effect on Bax expression. Besides, this flavonoid stimu- lated slight but significant inhibitory effects on Bcl-2 expression at mRNA levels. In sum, the encouraging consequences of using quercetin toward the U937 cells have made it a favorable compound for treating AML through the downregulation of anti-apoptotic proteins.