Lee Da Hyun, Kim Chang Gun, Lim Yoongho, Shin Soon Young
Department of Biological Sciences, College of Biological Science and Biotechnology, Konkuk University, Seoul 05029, Republic of Korea.
Division of Bioscience and Biotechnology, BMIC, Konkuk University, Seoul 05029, Republic of Korea.
Oncol Lett. 2017 Dec;14(6):6571-6577. doi: 10.3892/ol.2017.7023. Epub 2017 Sep 22.
Aurora kinase A (AURKA) is essential for regulating mitosis and is frequently amplified in various cancer cell types. However, the effect of AURKA inhibition on the induction of apoptosis remains unclear. In the present study, it was reported that treatment with TCS7010, a specific inhibitor of AURKA, resulted in the accumulation of cells in the sub-G/G phase of the cell cycle and increased the percentage of annexin V-binding cells. The cleavage of caspase-2, caspase-7, and poly(ADP-ribose)polymerase (PARP) significantly increased in a time-dependent manner following TCS7010 treatment. In addition, TCS7010 resulted in the production of reactive oxygen species (ROS) and stimulation of the unfolded protein response (UPR), leading to the upregulation of CCAAT/enhancer-binding protein-homologous protein (CHOP), and its downstream target BCL2 like 11 (BIM). Pretreatment with N-acetylcystein, a ROS scavenger, significantly abrogated TCS7010-induced accumulation of CHOP, BIM, cleaved caspase-7 and cleaved PARP. These results suggest that TCS7010 triggers apoptosis through the ROS-mediated UPR signaling pathway.
极光激酶A（AURKA）对于调节有丝分裂至关重要，并且在各种癌细胞类型中经常扩增。然而，AURKA抑制对凋亡诱导的影响仍不清楚。在本研究中，据报道，用AURKA的特异性抑制剂TCS7010处理导致细胞在细胞周期的亚G/G期积累，并增加了膜联蛋白V结合细胞的百分比。在TCS7010处理后，半胱天冬酶-2、半胱天冬酶-7和聚（ADP-核糖）聚合酶（PARP）的裂解以时间依赖性方式显著增加。此外，TCS7010导致活性氧（ROS）的产生和未折叠蛋白反应（UPR）的刺激，导致CCAAT/增强子结合蛋白同源蛋白（CHOP）及其下游靶点BCL2样11（BIM）的上调。用ROS清除剂N-乙酰半胱氨酸预处理显著消除了TCS7010诱导的CHOP、BIM、裂解的半胱天冬酶-7和裂解的PARP的积累。这些结果表明，TCS7010通过ROS介导的UPR信号通路触发凋亡。
