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| The ERK-MNK-eIF4F signaling pathway mediates TPDHT-induced A549 cell death in vitro and in vivo | |
| Guo, Chuanlong1,2; Hou, Yuzhen1,2; Yu, Xuemin3; Zhang, Fan1,2; Wu, Xiaochen1,2; Wu, Xianggen1,2; Wang, Lijun4 | |
| 2020-03-01 | |
| Source Publication | FOOD AND CHEMICAL TOXICOLOGY
 |
| ISSN | 0278-6915 |
| Volume | 137Pages:10 |
| Corresponding Author | Wu, Xianggen(wuxianggen@126.com) ; Wang, Lijun(wanglijun@qdio.ac.cn) |
| Abstract | 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. |
| Keyword | Apoptosis eIF4F ERK MNK A549 cells |
| DOI | 10.1016/j.fct.2020.111158 |
| Indexed By | SCI |
| Language | 英语 |
| Funding Project | National Natural Science Foundation of China[81773586] ; Talent Fund of Shandong Collaborative Innovation Center of Eco-Chemical Engineering[XTCXQN19] |
| WOS Research Area | Food Science & Technology ; Toxicology |
| WOS Subject | Food Science & Technology ; Toxicology |
| WOS ID | WOS:000517659300016 |
| Publisher | PERGAMON-ELSEVIER SCIENCE LTD |
| Citation statistics | |
| Document Type | 期刊论文 |
| Identifier | http://ir.qdio.ac.cn/handle/337002/165632 |
| Collection | 实验海洋生物学重点实验室 |
| Corresponding Author | Wu, Xianggen; Wang, Lijun |
| Affiliation | 1.Qingdao Univ Sci & Technol, Coll Chem Engn, Dept Pharm, Qingdao 266042, Peoples R China 2.Qingdao Univ Sci & Technol, Key Lab Pharmaceut Res Metab Dis, Qingdao, Peoples R China 3.Shandong Univ, Qilu Hosp, NHC Key Lab Otorhinolaryngol, Dept Otorhinolaryngol, Shandong 266035, Peoples R China 4.Chinese Acad Sci, Inst Oceanol, Key Lab Expt Marine Biol, Qingdao 266071, Peoples R China |
| Corresponding Author Affilication | Key Laboratory of Experimental Marine Biology, Institute of Oceanology, Chinese Academy of Sciences |
| Recommended Citation GB/T 7714 | Guo, Chuanlong,Hou, Yuzhen,Yu, Xuemin,et al. The ERK-MNK-eIF4F signaling pathway mediates TPDHT-induced A549 cell death in vitro and in vivo[J]. FOOD AND CHEMICAL TOXICOLOGY,2020,137:10. |
| APA | Guo, Chuanlong.,Hou, Yuzhen.,Yu, Xuemin.,Zhang, Fan.,Wu, Xiaochen.,...&Wang, Lijun.(2020).The ERK-MNK-eIF4F signaling pathway mediates TPDHT-induced A549 cell death in vitro and in vivo.FOOD AND CHEMICAL TOXICOLOGY,137,10. |
| MLA | Guo, Chuanlong,et al."The ERK-MNK-eIF4F signaling pathway mediates TPDHT-induced A549 cell death in vitro and in vivo".FOOD AND CHEMICAL TOXICOLOGY 137(2020):10. |
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