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

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.

Apoptosis; EGFR/ERK; ER stress; cell cycle; gastric cancer; myristicin; signaling pathway.