Wang Kun, Fu Xiao-Ting, Li Yuan, Hou Ya-Jun, Yang Ming-Feng, Sun Jing-Yi, Yi Shu-Ying, Fan Cun-Dong, Fu Xiao-Yan, Zhai Jing, Sun Bao-Liang
Department of Neurology, Shandong University School of Medicine, Jinan, 250012, Shandong, China.
Key Lab of Cerebral Microcirculation in Universities of Shandong, Taishan Medical University, Taian, 271000, Shandong, China.
Neurochem Res. 2016 Jun;41(6):1439-47. doi: 10.1007/s11064-016-1854-8. Epub 2016 Feb 4.
Selenocysteine (SeC) a natural available selenoamino acid exhibits novel anticancer activities against human cancer cell lines. However, the growth inhibitory effect and mechanism of SeC in human glioma cells remain unclear. The present study reveals that SeC time- and dose-dependently inhibited U251 and U87 human glioma cells growth by induction of S-phase cell cycle arrest, followed by the marked decrease of cyclin A. SeC-induced S-phase arrest was achieved by inducing DNA damage through triggering generation of reactive oxygen species (ROS) and superoxide anion, with concomitant increase of TUNEL-positive cells and induction of p21waf1/Cip1 and p53. SeC treatment also caused the activation of p38MAPK, JNK and ERK, and inactivation of AKT. Four inhibitors of MAPKs and AKT pathways further confirmed their roles in SeC-induced S-phase arrest in human glioma cells. Our findings advance the understanding on the molecular mechanisms of SeC in human glioma management.
硒代半胱氨酸（SeC）是一种天然存在的含硒氨基酸，对人类癌细胞系具有新型抗癌活性。然而，SeC对人胶质瘤细胞的生长抑制作用及其机制仍不清楚。本研究表明，SeC通过诱导S期细胞周期停滞，呈时间和剂量依赖性地抑制U251和U87人胶质瘤细胞的生长，随后细胞周期蛋白A显著减少。SeC诱导的S期停滞是通过触发活性氧（ROS）和超氧阴离子的产生来诱导DNA损伤实现的，同时TUNEL阳性细胞增加以及p21waf1/Cip1和p53的诱导。SeC处理还导致p38MAPK、JNK和ERK的激活以及AKT的失活。四种MAPKs和AKT途径抑制剂进一步证实了它们在SeC诱导人胶质瘤细胞S期停滞中的作用。我们的研究结果推进了对SeC在人类胶质瘤治疗中分子机制的理解。
