Emodin induces apoptosis in human hepatocellular carcinoma HepaRG cells via the mitochondrial caspase-dependent pathway

Dong, Xiaoxv; Ni, Boran; Fu, Jing; Yin, Xingbin; You, Longtai; Leng, Xin; Liang, Xiao; Ni, Jian

ROS are generated as by-products of mitochondrial respiration or precise oxidases and play an important role in apoptosis signaling. Stimulated ROS production could result in oxidative stress and induce cellular damage (43) . Emodin treatment effectively triggered production of intracellular ROS, which was reversed by pre-treatment with NAC. These results indicate that the change in intracellular ROS by emodin was at least in part related to apoptosis in the HepaRG cells. Furthermore, excessive ROS can induce oxidative DNA damage followed by cell cycle process arrest or delay (44) . In the present study, we found that the mechanism of action of emodin in HepaRG cells was similar to that of aloe-emodin, suggesting that cell cycle arrest might be one of the mechanisms underlying the cytotoxic effect on HepaRG cells induced by emodin (45) . Mitochondrial impairment or dysfunction could rapidly induce the inhibition of cell survival and proliferation (46) . Our data suggest that emodin induced the collapse of MMP with an increased release of cytochrome c from the mitochondria into the cytosol, indicating clearly that the mitochondria play an essential role in emodin-induced apoptosis of HepaRG cells. These results are in accordance with our previous study (45) , which demonstrated that aloe-emodin inhibited HepaRG proliferation by the induction of apoptosis through the intrinsic mitochondrial pathway.