J Cancer 2020; 11(2):500-507. doi:10.7150/jca.30381

Research Paper

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

Aili Wang1,2,3*, Huihong Jiang1,2,3*, Yuanyuan Liu1,2,3, Jing Chen1,2,3, Xue Zhou1,2,3, Chenxi Zhao1,2,3, Xia Chen1,2,3, Mobin Lin1,2,3✉

1. Center for clinical research and translational medicine, Yangpu hospital, Tongji University School of Medicine, Shanghai 200090, China.
2. Institute of Gastrointestinal Surgery and Translational Medicine, Tongji University School of Medicine, Shanghai 200090, China.
3. Department of General Surgery, Yangpu Hospital, Tongji University School of Medicine, Shanghai 200090, China.
*These authors contributed equally to this work.

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Citation:
Wang A, Jiang H, Liu Y, Chen J, Zhou X, Zhao C, Chen X, Lin M. Rhein induces liver cancer cells apoptosis via activating ROS-dependent JNK/Jun/caspase-3 signaling pathway. J Cancer 2020; 11(2):500-507. doi:10.7150/jca.30381. Available from http://www.jcancer.org/v11p0500.htm

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Abstract

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.

Keywords: Rhein, liver cancer, apoptosis, ROS, JNK/Jun/caspase-3 signaling pathway