Effect of Quercetin on apoptosis and autophagy through BAD and BCL-2 signaling pathway in human acute myeloid leukemia cell lines

Abstract

Acute myeloid leukemia (AML) is a hematopoietic malignant disease that common in the elderly. Current therapeutic approaches for AML have many side effects. For this reason, natural compounds are considered as alternative medicine. In the present study, we focus on anti-leukemic activity of quercetin, a natural flavonoid broadly founded in many plants and fruits. Our study founded that treatment of U937 cells with quercetin resulted in growth inhibition as well as decreased in cell viability in dose-dependent manner after 24 h of incubation. Apoptosis assay using annexin V and propidium iodide (PI) showed that quercetin significantly increased in the percentage of apoptotic cells. Moreover, exposure of U937 cells to quercetin augmented the expression of phosphatidylethanolamine conjugated form of microtubule-associated protein light chain 3 (LC3-II), a hallmark of autophagy. Furthermore, pretreatment of U937 cells with autophagy inhibitor, 3-Methyladenine (3-MA), dramatically enhanced quercetin-induced apoptotic cell death, indicated the cytoprotective role of autophagy in quercetin-treated AML cells. Western blot analysis was performed to investigate the expression of Bcl-2 family proteins, well-known modulators of apoptosis, after treated cells with quercetin. Results showed that quercetin downregulated the expression of Bcl-2 and phosphorylation levels of Bad and upregulated the expression of total Bad. In conclusion, our findings provided further basis of quercetin-mediated leukemic cell death and proposed that quercetin could be considered as a potent complementary medicine for AML treatment, particularly in combination with autophagy inhibitor.