Areca Nut Extract (ANE) Inhibits the Progression of Hepatocellular Carcinoma Cells Via Activation of ROS Production and Activation of Autophagy

Hepatocellular carcinoma (HCC) is a worldwide health problem. Currently, there is no effective therapeutic strategy for HCC patients. Chewing areca nut is closely associated with oral cancer and liver cirrhosis. The therapeutic effect of areca nut extract (ANE) on HCC is unknown. Our results revealed that ANE treatment caused a reduction in cell viability and an increase in cell apoptosis and suppressed tumor progression in xenograft models. ANE-treated didn't induce liver tumor in nude mice. For mechanism dissection, ANE treatment caused ROS-mediated autophagy and lysosome formation. Pretreatment with an ROS inhibitor, aminoguanidine hemisulfate (AGH), abolished ANE-induced ROS production. ANE treated cells caused an increase in light chain 3 (LC3)-I to -II conversion, anti-thymocyte globulin 5+12 (ATG5+12), and beclin levels, and apoptosis related-protein changes (an increases in BAX, cleaved poly(ADP-ribose) polymerase (c-PARP), and a decrease in the Bcl-2 level). In conclusion, our study demonstrated that the ANE may be a new potential compound for HCC therapy.