Aloe-emodin (1,8-dihydroxy-3-hydroxymethyl-anthraquinone) is one of the primary active compounds in total rhubarb anthraquinones isolated from some traditional medicinal plants such as Rheum palmatum L. and Cassia occidentalis, which induce hepatotoxicity in rats. Thus, the aim of this study was to determine the potential cytotoxic effects and the underlying mechanism of aloe-emodin on human normal liver HL-7702 cells. The CCK-8 assays demonstrated that aloe-emodin decreased the viability of HL-7702 cells in a dose-dependent and time-dependent manner. Aloe-emodin induced S and G2/M phase cell cycle arrest in HL-7702 cells. This apoptosis was further investigated by flow cytometry and nuclear morphological changes by DAPI staining, respectively. Moreover, aloe-emodin provoked the production of intracellular reactive oxygen species and the depolarization of mitochondrial membrane potential (MMP). Further studies by western blot indicated that aloe-emodin dose-dependently up-regulated the levels of Fas, p53, p21, Bax/Bcl-2 ratio, and cleaved caspase-3, -8, -9, and subsequent cleavage of poly(ADP-ribose)polymerase (PARP). Taken together, these results suggest that aloe-emodin inhibits cell proliferation of HL-7702 cells and induces cell cycle arrest and caspase-dependent apoptosis via both Fas death pathway and the mitochondrial pathway by generating reactive oxygen species, indicating that aloe-emodin should be taken into account in the risk assessment for human exposure. Copyright © 2017 John Wiley & Sons, Ltd.
Keywords: HL-7702 cells; ROS; aloe-emodin; apoptosis; hepatotoxicity.
Copyright © 2017 John Wiley & Sons, Ltd.