标题：The ERK-MNK-eIF4F signaling pathway mediates TPDHT-induced A549 cell death in vitro and in vivo
作者：Guo C.; Hou Y.; Yu X.; Zhang F.; Wu X.; Wu X.; Wang L.
作者机构：[Guo, C] Department of Pharmacy, College of Chemical Engineering, Qingdao University of Science and Technology, Qingdao, 266042, China, Key Laboratory 更多
通讯作者地址：[Wu, X] Department of Pharmacy, College of Chemical Engineering, Qingdao University of Science and TechnologyChina;
来源：Food and Chemical Toxicology
关键词：A549 cells; Apoptosis; eIF4F; ERK; MNK
摘要：The eIF4E/eIF4G complex plays a central role in gene expression regulation during the initial stage of translation. This study aimed to determine if the novel small molecule compound, TPDHT, could disrupt the interaction of eIF4E/eIF4G, and if it could exhibit excellent antitumor activity in vivo without causing apparent toxicity effect. This study investigated the antitumor mechanism of TPDHT in vitro and in vivo. TPDHT showed significant anti-proliferative activity on human lung cancer A549 cells, and it induced G0/G1 cycle arrest. Moreover, TPDHT also induced A549 cell apoptosis through the mitochondria-mediated apoptotic pathway. Our results indicate that TPDHT could disrupt the interaction of eIF4E/eIF4G, and the activity of eIF4F plays an important role in TPDHT-induced cell proliferation inhibition and apoptosis. Further research showed that TPDHT could inhibit the Ras/ERK/MNK pathway, and activation of the ERK pathway reversed TPDHT-induced cell proliferation inhibition and apoptosis. Taken together, our study findings indicated that TPDHT exerts an antitumor effect through an intrinsic apoptotic pathway controlled by the ERK/MNK/eIF4F pathway. © 2020 Elsevier Ltd