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Current Molecular Pharmacology

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ISSN (Print): 1874-4672
ISSN (Online): 1874-4702

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Research Article

Myristicin Suppresses Gastric Cancer Growth via _targeting the EGFR/ ERK Signaling Pathway

Author(s): Jin Song, Xiaolong Xu, Shasha He, Ning Wang, Yunjing Bai, Zhaoxia Chen, Bo Li* and Shengsheng Zhang*

Volume 16, Issue 7, 2023

Published on: 24 February, 2023

Article ID: e030123212339 Pages: 13

DOI: 10.2174/1874467216666230103104600

Price: $65

Abstract

Background: Myristicin is a type of natural compound showing anti-proliferative, anti-microbial, and anti-inflammatory effects. However, its role in gastric cancer treatment remains unknown.

Objective: In this study, the effect of myristicin on gastric cancer as well as its underlying mechanism was investigated.

Methods: Human gastric cancer cells were exposed to various concentrations of myristicin (0, 7.8125, 15.625, and 31.25 μM) for 48 h. Then CCK-8, fluorescence-activated cell sorting, and Hoechst staining were performed to evaluate the cell proliferation and apoptosis. The levels of proteins associated with cell cycle, apoptosis, endoplasmic reticulum (ER) stress, and EGFR/ERK signaling pathway were detected by western blot. JC-1 staining was conducted to determine the mitochondrial membrane potential. On the other hand, the effect of myristicin on gastric cancer growth and apoptosis was also determined in vivo.

Results: Myristicin retarded proliferation and induced ER stress and apoptosis in gastric cancer cells, with decreased expression of cyclins, increased Bax expression, activated caspases, and enhanced cytochrome C release and mitochondrial ROS. Furthermore, the EGFR/ERK signaling pathway was restrained by myristicin. In addition, EGFR over-expression abolished the inhibitory function of myristicin on proliferation, apoptosis, and ER stress. Also, myristicin inhibited the growth of gastric cancer cells as well as the EGFR/ERK signaling pathway in vivo.

Conclusion: Myristicin exerts an anti-cancer effect on gastric cancer cells by restraining the EGFR/ ERK signaling pathway. It may have the potential to be applied as a novel drug in gastric cancer treatment.

Keywords: Apoptosis, cell cycle, EGFR/ERK, ER stress, gastric cancer, myristicin, signaling pathway.

Graphical Abstract

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