The role of AMP-activated protein kinase in quercetin-induced apoptosis of HL-60 cells  

作　　者：Jie Xiao Guomin Niu Songmei Yin Shuangfeng Xie Yiqing Li Danian Nie Liping Ma Xiuju Wang Yudan Wu 

机构地区：[1]Department of Hematology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, China [2]Department of Hematology, People's Hospital in Nanhai District of Foshan City, Foshan 528200, China

出　　处：《Acta Biochimica et Biophysica Sinica》2014年第5期394-400,共7页生物化学与生物物理学报（英文版）

基　　金：This work was supported by the grant from the Natural Science Foundation of Guangdong Province （No. 9151008901000105）.

摘　　要：Our previous studies have shown that quercetin inhibits Cox-2 and Bcl-2 expressions, and induces human leukemia HL-60 cell apoptosis. In order to investigate the role of AMP-activated protein kinase （AMPK） on quercetin- induced apoptosis of HL-60 cells, we used flow cytometry to detect cell apoptosis. The expressions of LKB1, phosphorylated AMPK （p-AMPK）, and Cox-2 protein were detected in HL-60 cells and normal peripheral blood mono-nuclear cells （PBMCs） by western blot. The expressions of LKB1, p-AMPK, and Cox-2 were detected in HL-60 cells after culture with quercetin. The expressions of p-AMPK were detected in HL-60 cells after culture with AMPK inhibitor Compound C. Then, the expressions of LKB1, p-AMPK, and Cox-2 were detected in HL-60 cells after culture with quercetin alone or quercetin ＋ Compound C. It was found that there was no significant difference in LKB1 between PBMCs and HL-60. p-AMPK in PBMCs was higher than that in HL-60, while Cox-2 was lower. After culture of HL-60 with quercetin, p-AMPK was increased, Cox-2 was decreased, but LKB1 remained unchanged. After culture of HL-60 with Compound C, p-AMPK was decreased. There was no significant differ- ence in LKB1 between the quercetin-alone and the quercetin ＋ Compound C groups, p-AMPK decreased more significantly, while Cox-2 increased more significant- ly in the quercetin ＋ Compound C groups than those in the quercetin-alone groups. Taken together, these findings suggested that quercetin activates AMPK expression in HL-60 cells independent of LKB1 activation, inhibits Cox-2 expression by activating AMPK, and further regulates the Bcl-2-dependent pathways of apoptosis to exert its anti-leukemia effect.Our previous studies have shown that quercetin inhibits Cox-2 and Bcl-2 expressions, and induces human leukemia HL-60 cell apoptosis. In order to investigate the role of AMP-activated protein kinase （AMPK） on quercetin- induced apoptosis of HL-60 cells, we used flow cytometry to detect cell apoptosis. The expressions of LKB1, phosphorylated AMPK （p-AMPK）, and Cox-2 protein were detected in HL-60 cells and normal peripheral blood mono-nuclear cells （PBMCs） by western blot. The expressions of LKB1, p-AMPK, and Cox-2 were detected in HL-60 cells after culture with quercetin. The expressions of p-AMPK were detected in HL-60 cells after culture with AMPK inhibitor Compound C. Then, the expressions of LKB1, p-AMPK, and Cox-2 were detected in HL-60 cells after culture with quercetin alone or quercetin ＋ Compound C. It was found that there was no significant difference in LKB1 between PBMCs and HL-60. p-AMPK in PBMCs was higher than that in HL-60, while Cox-2 was lower. After culture of HL-60 with quercetin, p-AMPK was increased, Cox-2 was decreased, but LKB1 remained unchanged. After culture of HL-60 with Compound C, p-AMPK was decreased. There was no significant differ- ence in LKB1 between the quercetin-alone and the quercetin ＋ Compound C groups, p-AMPK decreased more significantly, while Cox-2 increased more significant- ly in the quercetin ＋ Compound C groups than those in the quercetin-alone groups. Taken together, these findings suggested that quercetin activates AMPK expression in HL-60 cells independent of LKB1 activation, inhibits Cox-2 expression by activating AMPK, and further regulates the Bcl-2-dependent pathways of apoptosis to exert its anti-leukemia effect.

关 键 词：LEUKEMIA QUERCETIN AMP-activated proteinkinase CYCLOOXYGENASE-2 

分 类 号：Q255[生物学—细胞生物学] Q55