Oleuropein induces apoptosis via activation of caspases and suppression of phosphatidylinositol 3-kinase/protein kinase B pathway in HepG2 human hepatoma cell line

Oleuropein is a polyphenol, that is found in extra-virgin olive oil. Previous studies have shown that oleuropein inhibits cell proliferation and induces apoptosis in breast cancer, colorectal cancer and thyroid cancer. The aim of the present study was to investigate the effects of oleuropein in hepatocellular carcinoma (HCC) cells. The results of Cell Counting Kit 8 and flow cytometric analysis indicated that oleuropein effectively inhibited cell viability and induced apoptosis in HepG2 human hepatoma cells in a dose-dependent manner, through activation of the caspase pathway. Proapoptotic Bcl-2 family members, BAX and Bcl-2, were involved in oleuropein-induced apoptosis. The phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) signaling pathway was also shown to be involved in this process. Oleuropein was demonstrated to suppress the expression of activated AKT. In addition, AKT overexpression promoted cell survival following treatment with oleuropein, while inhibition of AKT promoted cell death. Furthermore, the data demonstrated that oleuropein induces the production of reactive oxygen species (ROS) and that the function of oleuropein is, at least partially, ROS-dependent. These results suggest that oleuropein may be a promising novel chemotherapeutic agent in hepatocellular carcinoma.