Hesperidin Induced HePG-2 Cell Apoptosis through ROS-Mediated p53/Bcl-2/Bax and p-mTOR Signaling Pathways

Abstract

Recently, research showed that one of the most common kinds of liver cancer is hepatocellular carcinoma (HCC), which is also the fourth main cause of cancer deaths. In studies regarding chemicals to better treat the disease, hesperidin shows a novel potential in performing anticancer activities, particularly in liver cancer. However, the specific mechanism of hesperidin that causes such activities remains a mystery. Thus, the purpose of this study is to investigate hesperidin's effect on cell proliferation and activation of ROS-mediated signaling pathways in HePG-2 cells. Hesperidin shows a significant impact on inhibiting HePG-2 cells' proliferation through induction of cell apoptosis by Bcl-2, Bax, and p53 pathways. Treating cells with hesperidin in a dose-dependent manner shows a significant increase in the apoptotic cell population (sub-G1). Moreover, Hesperidin's induction of apoptotic activities shows dependence on ROS (reactive oxygen species) overproduction, further affecting the p-mTOR pathways and leading to DNA damage. Hence, the overall data demonstrate that ROS-mediated signaling pathways exhibit mechanisms that may lead to useful information for interpreting hesperidin-induced hepatocarcinoma cell apoptosis.