Cell Cycle Arrest, Apoptosis, and Autophagy Induced by Chabamide in Human Leukemia Cells

被引:9
|
作者
Hu, Kun [1 ]
Yang, Meng [1 ]
Xu, Yuan-yuan [1 ]
Wei, Kun [2 ]
Ren, Jie [1 ]
机构
[1] Changzhou Univ, Sch Pharmaceut Engn & Life Sci, Changzhou 213164, Peoples R China
[2] Yunnan Univ, Key Lab Med Chem Nat Resource, Minist Educ, Sch Chem Sci & Technol, Kunming 650091, Yunnan, Peoples R China
基金
中国国家自然科学基金;
关键词
apoptosis; autophagy; chabamide; cell cycle arrest; MAPKs;
D O I
10.1016/S1674-6384(16)60005-9
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
Objective To investigate the antitumor effect of chabamide in K562 (human leukemia cell line) cells. Methods The cytotoxicity was assessed by a standard colorimetric assay using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT). The morphological changes were observed by Hoechst 33258 staining. Induction of apoptosis, loss of the mitochondrial membrane potential (Delta Psi(m)), and cell cycle analysis were evaluated by flow cytometry (FCM) analysis. Levels of apoptosis-related proteins, cell cycle-related proteins, and LC3 protein were detected by Western blotting. Moreover, the autophagy induced by chabamide was also detected by MDC fluorescent staining. Results Chabamide significantly inhibited cell proliferation by cell cycle arrest in the G(0)/G(1) phase. This phenomenon was associated with an obvious increase in p21 expression and decrease in cyclin D-1 and cyclin-dependent kinase 2/4/6 protein expression. Moreover, chabamide could regulate the changes in mitochondrial membrane potential, increase the expression of apoptosis-related proteins, such as Bax and cytochrome C, and decrease the protein expression of Bcl-2, caspase-9, caspase-3, and PARP-1. JNK, ERK1/2, and p38 were also regulated by chabamide in K562 cells. Furthermore, induction of autophagy, marked by autophagic vacuole formation, was detected. Conversion of LC3-I to LC3-II, a marker of active autophagosome formation, was also detected following chabamide treatment. Conclusion The antitumor activity of chabamide with the results of apoptosis and autophagy induction was confirmed in K562 cells.
引用
收藏
页码:30 / 38
页数:9
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