4-Hydroxyderricin Promotes Apoptosis and Cell Cycle Arrest through Regulating PI3K/AKT/mTOR Pathway in Hepatocellular Cells

4-hydroxyderricin (4-HD), as a natural flavonoid compound derived from Angelica keiskei, has largely unknown inhibition and mechanisms on liver cancer. Herein, we investigated the inhibitory effects of 4-HD on hepatocellular carcinoma (HCC) cells and clarified the potential mechanisms by exploring apoptosis and cell cycle arrest mediated via the PI3K/AKT/mTOR signaling pathway. Our results show that 4-HD treatment dramatically decreased the survival rate and activities of HepG2 and Huh7 cells. The protein expressions of apoptosis-related genes significantly increased, while those related to the cell cycle were decreased by 4-HD. 4-HD also down-regulated PI3K, p-PI3K, p-AKT, and p-mTOR protein expression. Moreover, PI3K inhibitor (LY294002) enhanced the promoting effect of 4-HD on apoptosis and cell cycle arrest in HCC cells. Consequently, we demonstrate that 4-HD can suppress the proliferation of HCC cells by promoting the PI3K/AKT/mTOR signaling pathway mediated apoptosis and cell cycle arrest.