The role of AMP-activated protein kinase in quercetin-induced apoptosis of HL-60 cells.
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 mononuclear 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 difference in LKB1 between the quercetin-alone and the quercetin + Compound C groups. p-AMPK decreased more significantly, while Cox-2 increased more significantly 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.
Department of Hematology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, China.
Jie
J
Xiao
Guomin
G
Niu
Songmei
S
Yin
Shuangfeng
S
Xie
Yiqing
Y
Li
Danian
D
Nie
Liping
L
Ma
Xiuju
X
Wang
Yudan
Y
Wu
D055372:AMP-Activated Protein Kinases / Q000378:metabolism* / Q000502:physiology; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D005434:Flow Cytometry; D018922:HL-60 Cells; D006801:Humans; D011794:Quercetin / Q000494:pharmacology*
D011794:Quercetin; D055372:AMP-Activated Protein Kinases
AMP-activated protein kinase; cyclooxygenase-2; leukemia; quercetin