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

IF 2.4 4区 生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY
Jin Song, Xiaolong Xu, Shasha He, Ning Wang, Yunjing Bai, Zhaoxia Chen, Bo Li, Shengsheng Zhang
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引用次数: 2

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.

肉豆蔻素通过靶向EGFR/ ERK信号通路抑制胃癌生长。
背景:肉豆蔻素是一种具有抗增殖、抗微生物和抗炎作用的天然化合物。然而,其在胃癌治疗中的作用尚不清楚。目的:探讨肉豆蔻素对胃癌的作用及其机制。方法:将人胃癌细胞暴露于不同浓度的肉豆素(0、7.8125、15.625、31.25 μM)中48 h,采用CCK-8、荧光活化细胞分选、Hoechst染色法观察细胞增殖和凋亡情况。western blot检测与细胞周期、凋亡、内质网应激和EGFR/ERK信号通路相关的蛋白水平。JC-1染色测定线粒体膜电位。另一方面,我们还在体内研究了肉豆蔻素对胃癌生长和凋亡的影响。结果:肉豆蔻素延缓胃癌细胞增殖,诱导内质网应激和凋亡,降低细胞周期蛋白表达,增加Bax表达,激活半胱天冬酶,增强细胞色素C释放和线粒体ROS。此外,EGFR/ERK信号通路受到肉豆蔻素的抑制。此外,EGFR过表达可消除肉豆蔻素对细胞增殖、凋亡和内质网应激的抑制作用。此外,肉豆蔻素在体内抑制胃癌细胞的生长以及EGFR/ERK信号通路。结论:肉豆蔻素通过抑制EGFR/ ERK信号通路对胃癌细胞具有抗癌作用。它有可能作为一种新型药物应用于胃癌的治疗。
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来源期刊
Current molecular pharmacology
Current molecular pharmacology Pharmacology, Toxicology and Pharmaceutics-Drug Discovery
CiteScore
4.90
自引率
3.70%
发文量
112
期刊介绍: Current Molecular Pharmacology aims to publish the latest developments in cellular and molecular pharmacology with a major emphasis on the mechanism of action of novel drugs under development, innovative pharmacological technologies, cell signaling, transduction pathway analysis, genomics, proteomics, and metabonomics applications to drug action. An additional focus will be the way in which normal biological function is illuminated by knowledge of the action of drugs at the cellular and molecular level. The journal publishes full-length/mini reviews, original research articles and thematic issues on molecular pharmacology. Current Molecular Pharmacology is an essential journal for every scientist who is involved in drug design and discovery, target identification, target validation, preclinical and clinical development of drugs therapeutically useful in human disease.
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