Ginsenoside Rg5 induces apoptosis in human esophageal cancer cells through the phosphoinositide-3 kinase/protein kinase B signaling pathway

The role of ginsenoside in the prevention of cancer has been well established. Ginsenoside Rg5 is one of the main components isolated from red ginseng, which has been demonstrated to have anti-tumor effects by inhibiting cell proliferation and causing DNA damage. However, the role of ginsenoside Rg5 and its molecular mechanisms remain unclear in human esophageal cancer. In the present study, Rg5 was investigated as a novel drug for the chemotherapy of esophageal cancer in in vitro experiments. Esophageal cancer Eca109 cells were exposed to various concentrations of ginsenoside Rg5 (0–32 µΜ) for 24 h. Subsequent cell proliferation assays demonstrated that treatment with ginsenoside Rg5 resulted in the dose-dependent inhibition of proliferation, while a significant increase in apoptotic rate and increased activities of caspase-3, −8 and −9 were observed. In addition, the mitochondrial membrane potential was decreased and the cytoplasmic free calcium level increased following treatment with ginsenoside Rg5. Furthermore, the expression of B-cell lymphoma 2 and phosphorylated-protein kinase B (p-Akt) decreased. The specific phosphoinositide-3 kinase (PI3K) inhibitor LY294002 promoted this effect, while insulin-like growth factor-1, a specific PI3K activator, inhibited this action. Taken together, the results suggested that ginsenoside Rg5 may have a tumor-suppressive effect on esophageal cancer by promoting apoptosis and may be associated with the downregulation of the PI3K/Akt signaling pathway.