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Background: Liver cancer is one of the leading cancers in China. Rhein induces apoptosis in various human cancer cells, but the underlying mechanism is still unknown. Methods: In the present study, the MTT assay was used to detect the anti-cell growth ability of Rhein on liver cancer cells. Hoechst33342 staining and FACS assay were used to detect cell apoptosis. Finally, the effect of Rhein on JNK protein' phosphorylation level and the apoptosis-associated proteins were determined by western blot. Results: Here, we found that Rhein significantly inhibited the cell viability in a dose-dependent and time-dependent manner both in HepG2 and Huh7 cells. Also, Rhein increased the apoptosis, mitochondrial membrane potential (MMP) and cell-cycle arrest. Furthermore, we observed that the ROS level and JNK/Jun/caspase-3 signaling pathway played a key role in Rhein induced apoptosis. Our study further demonstrated that Rhein increases apoptosis by inducing the generation of ROS and activating the JNK/Jun/caspase-3 signaling pathway. Conclusions: The present study showed that Rhein promotes apoptosis via regulating ROS/JNK/Jun/caspase-3 signaling pathway both in HepG2 and Huh7 cells. Rhein may be a promising therapeutic candidate for the treatment of liver cancer.

Rhein induces liver cancer cells apoptosis via activating ROS-dependent JNK/Jun/caspase-3 signaling pathway