Quercetin-induced apoptosis of HL-60 cells by reducing PI3K/Akt
Quercetin-induced apoptosis of HL-60 cells by reducing PI3K/Akt
复制标题
槲皮素通过降低 PI3K/Akt 诱导 HL-60 细胞凋亡
DOI：
10.1007/s11033-012-1621-0
复制
发表时间：
2012-07-01
影响因子：
2.8
通讯作者：
Zou Chan
中科院分区：
文献类型：
--
作者：
Zhang Yuan;Chen Long;Zou Chan
探讨槲皮素对白血病细胞增殖和凋亡的影响及机制，为其临床应用提供理论依据。不同剂量槲皮素处理HL-60白血病细胞系，MTT法评估白血病细胞的增殖活性；采用Hoechst 33258荧光染色观察HL-60细胞凋亡形态学变化，包括核固缩、DNA断裂等；流式细胞仪检测细胞凋亡率和caspase 2,3活化情况；Western blotting检测细胞信号通路磷脂酰肌醇3激酶（PI3K）、磷酸化蛋白激酶B（pAkt）、Bcl-2、Bax。槲皮素可通过阻断G0/G1期显着降低HL-60细胞的增殖活性，并以时间和剂量依赖性方式诱导HL-60细胞凋亡。槲皮素通过降低 PI3K 和 Bax 的蛋白表达、抑制 Akt 的磷酸化、降低 Bcl-2 蛋白的水平、增加 caspase-2 和 -3 的激活以及增加聚 (ADP-核糖) 聚合酶裂解而引起白血病细胞凋亡。我们的结果表明，槲皮素引起的细胞凋亡过程是通过 HL-60 细胞中 pAkt 和 Bcl-2 水平的降低、Bax 水平的增加以及 caspase 家族的激活介导的。
To explore the effect and mechanism of quercetin on proliferation and apoptosis of leukemia cells, and provide a theoretical basis for its clinical application. HL-60 leukemia cell lines was treated with different dose quercetin, the proliferation activity of leukemia cells was assessed by MTT method; the morphological changes of apoptosis of HL-60 cells, including nuclear condensation and DNA fragmentation, were observed by Hoechst 33258 fluorescence staining, the apoptosis rate and caspase 2,3 activation were assessed by flow cytometry, and the cell signal pathway including phosphatidylinositol 3-kinase (PI3K), phosphorylated protein kinase B (pAkt), Bcl-2, Bax were detected by western blotting. Quercetin could significantly decrease the proliferation activity of HL-60 cells through the blockade of G0/G1phase, and induce the apoptosis of HL-60 cells in a time- and dose-dependent manner. Quercetin caused leukemia cells apoptosis by decreasing the protein expression of PI3K and Bax, the inhibitory phosphorylation of Akt, the decreased levels of Bcl-2 protein and increased activations of caspase-2 and -3, and increased poly(ADP-ribose) polymerase cleavage. Our results indicate that the apoptotic processes caused by quercetin are mediated by the decrease of pAkt and Bcl-2 levels, the increase of Bax level, and the activation of caspase families in HL-60 cells.