Synergic effect of the combination of isoliquiritigenin and aresnic trioxide in HepG2 liver cancer cells

Despite continuous therapeutic interventions, the prognosis of hepatocellular carcinoma (HCC) remains very poor. Thus, quest for novel treatment strategies to improve therapeutic window of HCC therapy is paramount. Arsenic trioxide (ATO) is commonly used as the first-line treatment for acute promyelocytic leukemia (APL). Isoliquiritigenin (ISL) is a potential plant-based bioactive molecule with versatile biological and pharmacological effects including anticancer effect. The present study aimed to investigate the potential synergistic effects of combination of ISL and ATO in HCC cells. The data revealed that the combination of ISL and ATO synergistically inhibited HCC cell proliferation. The collective data demonstrate that synergistic anticancer effect of combined treatment of ISL + ATO was achieved via cooperative induction of mitochondrial apoptosis through ROS generation and inhibition of PI3K/Akt/mTOR pathway. In addition, ROS generation and suppression of PI3K/Akt/mTOR pathway were found to be two independent events in induction of apoptosis. Finally, we observed that combination treatment effectively suppressed tumor growth in nude mice xenograft model through induction of intrinsic apoptosis and inhibition of PI3K/Akt/mTOR pathway. In conclusion, the findings of this study suggest that both drugs work synergistically to exert anti-tumor effect in HCC, both in-vitro and in-vivo and could offer novel strategy for liver cancer treatment.