Chen Jin-Cherng, Hwang Juen-Haur, Chiu Wen-Hsuan, Chan Yin-Ching
a Department of Neurosurgery, Dalin Tzu Chi Hospital, Dalin, Chiayi, Taiwan and School of Medicine , Tzu Chi University , Hualien , Taiwan.
Nutr Cancer. 2014;66(4):700-6. doi: 10.1080/01635581.2014.902974. Epub 2014 Apr 16.
Viability, cell cycle distribution, and expressions of eukaryotic translation initiation factor-2α (eIF-2α), cyclin D1, poly(ADP-ribose) polymerase 1 (PARP-1), and apoptosis-inducing factor (AIF) of RT-2 glioma cells were assayed under treatment of tetrandrine and caffeine for 48 h. The results showed that cell viability decreased significantly under treatment with tetrandrine (5 μM) alone or under combined treatment with tetrandrine (5 μM) and caffeine (0.5 or 1 mM). The ratio of RT-2 cells at sub G1 and G0/G1 stages increased significantly during combined treatment of tetrandrine (5 μM) and caffeine (0.5, 1 mM). The ratio of phospharylated eIF-2α to dephospharylated eIF-2α increased, whereas cyclin D1 decreased significantly under combined treatment of tetrandrine (5 μM) and caffeine (1 mM). The cleaved PARP-1 to PARP-1 ratio was elevated significantly under treatment of 5 μM tetrandrine alone, and combined treatment of 5 μM tetrandrine and caffeine (0.5, 1 mM). The expression levels of AIF increased significantly under treatment of 5 μM tetrandrine alone or 1 mM caffeine alone, and combined treatment of 5 μM tetrandrine and caffeine (0.5, 1 mM). In conclusion, tetrandrine and caffeine could induce glioma cell death possibly via increasing eIF-2α phospharylation, decreasing cyclin-D1 expression, and increasing caspase-dependent and -independent apoptosis pathways.
在汉防己甲素和咖啡因处理48小时的条件下，检测RT-2胶质瘤细胞的活力、细胞周期分布以及真核翻译起始因子-2α（eIF-2α）、细胞周期蛋白D1、聚（ADP-核糖）聚合酶1（PARP-1）和凋亡诱导因子（AIF）的表达。结果显示，单独用汉防己甲素（5μM）处理或汉防己甲素（5μM）与咖啡因（0.5或1mM）联合处理时，细胞活力显著降低。在汉防己甲素（5μM）与咖啡因（0.5、1mM）联合处理期间，RT-2细胞处于亚G1期和G0/G1期的比例显著增加。在汉防己甲素（5μM）与咖啡因（1mM）联合处理时，磷酸化eIF-2α与去磷酸化eIF-2α的比例增加，而细胞周期蛋白D1显著降低。单独用5μM汉防己甲素处理以及5μM汉防己甲素与咖啡因（0.5、1mM）联合处理时，裂解的PARP-1与PARP-1的比例显著升高。单独用5μM汉防己甲素处理、单独用1mM咖啡因处理以及5μM汉防己甲素与咖啡因（0.5、1mM）联合处理时，AIF的表达水平均显著增加。总之，汉防己甲素和咖啡因可能通过增加eIF-2α磷酸化、降低细胞周期蛋白D1表达以及增加半胱天冬酶依赖性和非依赖性凋亡途径来诱导胶质瘤细胞死亡。
