Hu Xiu-Wei, Chien Ching-Ming, Yang Sheng-Huei, Lin Yi-Hsiung, Lu Chih-Ming, Chen Yeh-Long, Lin Shinne-Ren
Faculty of Medicinal and Applied Chemistry, Kaohsiung Medical University, Kaohsiung, Taiwan, 807, ROC.
Cell Biol Toxicol. 2006 Nov;22(6):417-27. doi: 10.1007/s10565-006-0098-9. Epub 2006 Aug 13.
N'-(11H-indolo[3,2-c]quinolin-6-yl)-N,N-dimethylethane-1,2-diamine (IQDMA), an indoloquinoline compound, was identified in our laboratory as a novel antineoplastic agent with a broad spectrum of antitumor activity against many human cancer cells. Cell cycle analysis showed S-phase arrest and induction of apoptosis in HL-60 cells following 24 h exposure to IQDMA. Analysis of the cell cycle regulatory proteins demonstrated that IQDMA did not change the steady-state levels of cyclin B1, cyclin D3, and p21, but decreased the protein levels of Cdk1, Cdk2, and cyclin A. IQDMA also caused a marked increase in apoptosis, which was accompanied by increased levels of Bax, activated caspase-3, -8, and -9, and cleaved PARP. These molecular alterations provide an insight into IQDMA-caused growth inhibition, S-phase arrest, and apoptotic death of HL-60 cells.
N'-(11H-吲哚并[3,2-c]喹啉-6-基)-N,N-二甲基乙烷-1,2-二胺（IQDMA）是一种吲哚喹啉化合物，在我们实验室中被鉴定为一种新型抗肿瘤药物，对多种人类癌细胞具有广泛的抗肿瘤活性。细胞周期分析显示，HL-60细胞在暴露于IQDMA 24小时后出现S期阻滞并诱导凋亡。对细胞周期调节蛋白的分析表明，IQDMA并未改变细胞周期蛋白B1、细胞周期蛋白D3和p21的稳态水平，但降低了细胞周期蛋白依赖性激酶1（Cdk1）、细胞周期蛋白依赖性激酶2（Cdk2）和细胞周期蛋白A的蛋白水平。IQDMA还导致凋亡显著增加，同时伴有Bax水平升高、半胱天冬酶-3、-8和-9激活以及聚（ADP-核糖）聚合酶（PARP）裂解。这些分子改变为IQDMA导致HL-60细胞生长抑制、S期阻滞和凋亡死亡提供了深入了解。
