Ginsenoside induces apoptosis, autophagy and cell cycle arrest in gastric cancer cells by regulation of reactive oxygen species and activation of MAPK pathway

Abstract

Purpose: To study the influence of ginsenoside on apoptosis, cell cycle and autophagy in gastric carcinoma (GC), and its effect on reactive oxygen species (ROS) levels and the mitogen-activated protein kinase (MAPK) pathway. 
 Methods: Human gastric cancer cell line BGC-823 was randomly divided into the following groups: control, 100 μM ginsenoside (Rg5), 150 μM Rg5, and 200 μM Rg5 groups. Western blot assay was used to determine the expressions of autophagy-associated protein 12 (Atg12), Beclin-1, lc3b II, cycle-related protein, phosphated mitotic cyclin 25 homologous protein C (p-cdc25c), cyclin B1, and MAPK signaling pathway-related proteins. 
 Results: There was significantly higher apoptosis in Rg5-treated BGC-823 cells than in untreated cells. Relative protein levels of Beclin-1, Atg5, Atg12, and lc3b II in BGC-823 cells in Rg5 groups were significantly and concentration-dependently up-regulated, relative to the corresponding expression levels in untreated cells. There were markedly up-regulated proteins of p-cdc25c, cyclin B1 and p-cdc2 in Rg5-exposed BGC-823 cells than in untreated cells, while CDC2 protein expression was significantly and concentration-dependently lower than that of control group (p < 0.05). Rg5 treatment resulted in marked and concentration-dependent increases in ROS levels in BGC-823 cells, relative to control cells (p < 0.05), whereas the expression levels of p-p38, p-JNK and p-ERK were significantly higher in Rg5-exposed cells than in unexposed cells (p < 0.05). 
 Conclusion: Ginsenoside induces apoptosis, autophagy and cycle interruption in GC cells by regulating ROS production and activating MAPK pathway. Therefore, ginsenoside may be a promising agent for the management of gastric cancer. However, there is a need to conduct in vivo studies on the compound.