Wu Zchong-Zcho, Chien Ching-Ming, Yang Sheng-Huei, Lin Yi-Hsiung, Hu Xiu-Wei, Lu Yu-Jhang, Wu Ming-Jung, Lin Shinne-Ren
Faculty of Medicinal and Applied Chemistry, Kaohsiung Medical University, Kaohsiung 807, Taiwan, ROC.
Mol Cell Biochem. 2006 Nov;292(1-2):99-105. doi: 10.1007/s11010-006-9222-7. Epub 2006 May 30.
We studied the effect of 2-(6-(2-thieanisyl)-3(Z)-hexen-1,5-diynyl)aniline(THDA), a newly developed anti-cancer agent, on cell proliferation, cell cycle progression, and induction of apoptosis in K562 cells. THDA was found to inhibit the growth of K562 cells in a time-and dose-dependent manner. Cell cycle analysis showed G2/M phase arrest and apoptosis in K562 cells following 24 h exposure to THDA. During the G2/M arrest, cyclin-dependent kinase inhibitors (CDKIs), p21 and p27 were increased in a time-dependent manner. Analysis of the cell cycle regulatory proteins demonstrated that THDA did not change the steady-state levels of cyclin B1, cyclin D3 and Cdc25C, but decreased the protein levels of Cdk1, Cdk2 and cyclin A. THDA also caused a marked increase in apoptosis, which was associated with activation of caspase-3 and proteolytic cleavage of poly (ADP-ribose) polymerase. These molecular alterations provide an insight into THDA-caused growth inhibition, G2/M arrest and apoptotic death of K562 cells.
我们研究了新开发的抗癌药物2-(6-(2-噻吩甲酰基)-3(Z)-己烯-1,5-二炔基)苯胺(THDA)对K562细胞增殖、细胞周期进程及凋亡诱导的影响。发现THDA以时间和剂量依赖性方式抑制K562细胞的生长。细胞周期分析显示，K562细胞在暴露于THDA 24小时后出现G2/M期阻滞和凋亡。在G2/M阻滞期间，细胞周期蛋白依赖性激酶抑制剂(CDKIs)，p21和p27呈时间依赖性增加。对细胞周期调节蛋白的分析表明，THDA并未改变细胞周期蛋白B1、细胞周期蛋白D3和Cdc25C的稳态水平，但降低了Cdk1、Cdk2和细胞周期蛋白A的蛋白水平。THDA还导致凋亡显著增加，这与caspase-3的激活及聚(ADP-核糖)聚合酶的蛋白水解裂解有关。这些分子改变为THDA导致K562细胞生长抑制、G2/M阻滞和凋亡死亡提供了深入了解。
