Objective: Melatonin exhibits numerous anti-cancer activities in the treatment of human cancers. Nevertheless, the mechanisms of anti-gastric cancer effect of melatonin is still unclear. The aim of the study is to investigate the interaction between melatonin, endoplasmic reticulum (ER) stress, NF-κB signaling and HSF1 protein in gastric cancer cells.
Methods: In the current study, we used CCK-8, flow cytometry and Western blot to research anticancer mechanism of melatonin in AGS cells.
Results: The data demonstrated that melatonin could suppress cell proliferation and increase cell apoptosis. We explore that the ER stress and NF-kB signaling pathways play crucial roles in the cell apoptosis process. Of note, melatonin increased the expression of p-PERK and p-eIF2α, and decreased the expression of p-P65 and p-IκBα. A combination of melatonin and PERK inhibitor (GSK2606414) or NF-κB inhibitor (Bay11-7082) suppressed the activation PERK/eIF2α and NF-κB signaling pathway. Subsequently, the expression of HSF1 protein was upregulated by melatonin and kept its expression by Bay 11-7082.
Conclusion: These results suggest that melatonin induces AGS cell apoptosis by up-regulating PERK/eIF2α and downregulating NF-κB signaling pathway.
Keywords: HSF1; NF-κB; PERK/eIF2α; apoptosis; gastric cancer; melatonin.
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