Hispidulin Induces Apoptosis Through Mitochondrial Dysfunction and Inhibition of P13k/Akt Signalling Pathway in HepG2 Cancer Cells

Hispidulin is a flavonoid compound which is an active ingredient in a number of traditional Chinese medicinal herbs. However, it's therapeutic activity remains poorly understood. The present study investigated the pro-apoptotic effects and mechanism by which Hispidulin induces apoptosis in human hepatoblastoma cancer (HepG2) cells. The results showed that Hispidulin induced cell death in a dose- and time-dependent manner in HepG2 cells whereas no toxic reaction was observed in normal human liver cells at indicated concentration. This study also demonstrated that Hispidulin induces apoptosis through mitochondrial dysfunction, which is characterized by decreased Bcl-2/Bax ratio, disrupted mitochondrial membrane potential and increased release of cytochrome C and activated capase-3. Our results also showed that mitochondrial dysfunction was triggered by Hispidulin-induced excessive ROS generation. Hispidulin also significantly inhibited Akt activation. ROS inhibitor NAC abrogated the inhibitory effect of Hispidulin on P13k/Akt signalling pathway and the proapoptotic effect in HepG2 cells. Our results demonstrate for the first time that Hispidulin induces apoptosis in HepG2 cells and suggested that the pro-apoptotic effect of Hispidulin was mediated through mitochondrial dysfunction and inhibition of P13k/Akt signalling pathway. Since no toxic effect was observed when normal liver cells were treated with Hispidulin, Hispidulin may have the potential to be used as therapeutic for liver cancer.