Effects Of Quercetin On AML Cells Mediated By Regulating Cell Energy Metabolism

Objective To analyze the effects of quercetin on the activity of acute myeloid leukemia cell lines HL-60 and KG-1α,and to further explore the possible metabolic mechanisms.Methods CCK-8 analysis was used to detect the prohibitive effects of quercetin on the proliferation of HL-60 and KG-1α cells,and flow cytometry was used to analyze measure the apoptosis;Quantitative real time polymerase chain reaction(q RT-PCR)was used to detect the gene expression changes of AMPK,CPT1 A and GLUT1,the key enzymes of cell energy metabolism;The contents of ATP and pyruvate were measured to determine the level of aerobic glycolysis.Results CCK-8 analysis showed that under different concentrations,the quercetin had a statistically significant inhibitory effect on the proliferation of HL-60 and KG-1α cells after 0,24,48 and 72 hours,respectively.The inhibitory effect of quercetin on the proliferation of HL-60 and KG-1α cells was concentration-and time-dependent(P < 0.05);The flow cytometry results displayed that quercetin promoted the apoptosis of HL-60 and KG-1α cells in a certain concentration and time range,but the total apoptosis rate of HL-60 cells was higher than that of KG-1α cells,and the apoptosis rates were more remarkable with the increase of quercetin concentration(the total apoptosis rate was more than 90%);q RT-PCR results demonstrated that compared with the black control group,quercetin decreased the expression of AMPK gene in KG-1α cells after 48 hours to affect cell energy metabolism(P <0.05),while it decreased the expression of AMPK gene in HL-60 cells after 6 hours,however,no significant difference compared with the control group.Additionally,quercetin significantly reduced the expression of CPT1 A gene in KG-1α cells after 48 hours to reduce the level of fatty acid oxidation(P = 0.0043).However,quercetin had the opposite effect after treating HL-60 cells,and the expression level of CPT1 A gene was higher than that of the control group.Quercetin also decreased the expression of GLUT1 gene in HL-60 and KG-1αcells in a time-dependent manner(P < 0.0001),and quercetin significantly reduced the contents of ATP and pyruvate in HL-60 and KG-1α cells in a certain time and concentration range(P < 0.0001).Conclusion Quercetin inhibited the proliferation of AML cells in a time-and concentration-dependent manner and promoted cell apoptosis rates.It might affect glucose uptake by inhibiting the expression of GLUT1,so as to reduce the production of ATP and pyruvate,and reduce the level of aerobic glycolysis.In addition,quercetin might also inhibit the expression of rate limiting enzyme CPT1 A in the process of fatty acid oxidation(FAO)and affect the oxidation capacity of fatty acids into mitochondria to meet the energy required for cell survival.This experiment preliminarily explored the potential molecular mechanism of quercetin in killing AML cells by inhibiting energy metabolism such as aerobic glucose degradation of AML cells,so as to provide theoretical and experimental basis for improving the treatment of AML.