Arginine methyltransferase inhibitor 1 inhibits gastric cancer by downregulating eIF4E and targeting PRMT5.

Abstract

Arginine methylation is carried out by protein arginine methyltransferase (PRMTs) family. Arginine methyltransferase inhibitor 1 (AMI-1) is mainly used to inhibit type I PRMT activity in vitro. However, the effects of AMI-1 on type II PRMT5 activity and gastric cancer (GC) remain unclear. In this study, we provided the first evidence that AMI-1 significantly inhibited GC cell proliferation and migration while induced GC cell apoptosis, and reduced the expression of PRMT5, eukaryotic translation initiation factor 4E (eIF4E), symmetric dimethylation of histone 3 (H3R8me2s) and histone 4 (H4R3me2s). In addition, AMI-1 inhibited tumor growth, downregulated eIF4E, H4R3me2s and H3R8me2s expression in mice xenografts model of GC. Collectively, our results suggest that AMI-1 inhibits GC by downregulating eIF4E and targeting type II PRMT5.

• Authors: Baolai Zhang, Su Zhang, Lijuan Zhu, Xue Chen, Yunfeng Zhao, Li Chao, Juanping Zhou, Xing Wang, Xinyang Zhang, Nengqian Ma
• Journal: Toxicology and applied pharmacology (Toxicol Appl Pharmacol) Vol. 336 Pg. 1-7 (12 01 2017) ISSN: 1096-0333 [Electronic] United States
• PMID: 28987382 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2017 Elsevier Inc. All rights reserved.

Chemical References

• Antineoplastic Agents
• Enzyme Inhibitors
• Eukaryotic Initiation Factor-4E
• Histones
• Repressor Proteins
• eIF4E protein, mouse
• PRMT1 protein, human
• PRMT5 protein, human
• Prmt1 protein, mouse
• Prmt5 protein, mouse
• Protein-Arginine N-Methyltransferases

Topics

• Animals
• Antineoplastic Agents (pharmacology)
• Apoptosis (drug effects)
• Cell Line, Tumor
• Cell Movement (drug effects)
• Cell Proliferation (drug effects)
• Dose-Response Relationship, Drug
• Down-Regulation
• Enzyme Inhibitors (pharmacology)
• Eukaryotic Initiation Factor-4E (metabolism)
• Female
• Histones (metabolism)
• Humans
• Mice, Inbred BALB C
• Mice, Nude
• Protein-Arginine N-Methyltransferases (antagonists & inhibitors, metabolism)
• Repressor Proteins (antagonists & inhibitors, metabolism)
• Signal Transduction (drug effects)
• Stomach Neoplasms (drug therapy, enzymology, pathology)
• Time Factors
• Tumor Burden (drug effects)