Lithium Chloride Promotes Apoptosis in Human Leukemia NB4 Cells by Inhibiting Glycogen Synthase Kinase-3 Beta.
Lithium Chloride Promotes Apoptosis in Human Leukemia NB4 Cells by Inhibiting Glycogen Synthase Kinase-3 Beta.
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DOI：
10.7150/ijms.12429
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发表时间：
2015
影响因子：
3.6
通讯作者：
Liu BZ
中科院分区：
文献类型：
--
作者：
Li L;Song H;Zhong L;Yang R;Yang XQ;Jiang KL;Liu BZ
急性早幼粒细胞白血病(APL)是急性髓系白血病(AML)的一个亚型。随着全反式维甲酸(ATRA)和三氧化二砷(ATO)的应用，APL成为预后最好的白血病之一。然而，ATRA和ATO并不是对所有的APL都有效。因此，APL的治疗需要一种新的策略。在这里，我们研究了用于治疗精神疾病的药物氯化锂(LiCl)是否能促进人类白血病NB4细胞的凋亡。我们观察到LiCl处理后NB4细胞的凋亡明显加快，并导致细胞周期停滞于G2/M期。此外，氯化锂还以剂量依赖的方式显著增加血清9磷酸化糖原合成酶激酶3β(p-GSK-3β)水平，降低AKT1蛋白水平。此外，氯化锂对c-myc的抑制也促进了细胞死亡，并伴随着β-catnin的增加。综上所述，这些结果表明，氯化锂通过Akt信号通路促进NB4细胞的凋亡，并通过增加p-GSK-3β(S9)诱导G2/M期停滞。
Acute promyelocytic leukemia (APL) is a subtype of acute myeloid leukemia (AML). With the application of all-trans retinoic acid (ATRA) and arsenic trioxide (ATO), APL becomes one of best prognosis of leukemia. However, ATRA and ATO are not effective against all APLs. Therefore, a new strategy for APL treatment is necessary. Here, we investigated whether lithium chloride (LiCl), a drug used for the treatment of mental illness, could promote apoptosis in human leukemia NB4 cells. We observed that treatment with LiCl significantly accelerated apoptosis in NB4 cells and led to cell cycle arrest at G2/M phase. Moreover, LiCl significantly increased the level of Ser9-phosphorylated glycogen synthase kinase 3β(p-GSK-3β), and decreased the level of Akt1 protein in a dose-dependent manner. In addition, LiCl inhibition of c-Myc also enhanced cell death with a concomitant increase in β-catnin. Taken together, these findings demonstrated that LiCl promoted apoptosis in NB4 cells through the Akt signaling pathway and that G2/M phase arrest was induced by increase of p-GSK-3β(S9).