L-Selenocysteine induced HepG-2 cells apoptosis through reactive oxygen species-mediated signaling pathway

• Published in: Molecular biology reports 2022-09, Vol.49 (9), p.8381-8390
• Main Authors: Zhang, Kaiying, Su, Jingyao, Chen, Danyang, Lin, Binger, Wu, Yucan, Wang, Yibing, Lei, Jiapei, Zheng, Ruilin, Zhu, Bing, Li, Yinghua
• Format: Article
• Language: English
• Subjects: Animal Anatomy; Animal Biochemistry; Apoptosis; Bcl-2 protein; Biomedical and Life Sciences; Caspase-3; Cell proliferation; Cell viability; Cholecystokinin; Cytotoxicity; DNA damage; DNA fragmentation; Electron microscopy; Flow cytometry; Histology; Life Sciences; Liver cancer; Mitochondria; Morphology; Original Article; Reactive oxygen species; Selenocysteine; Signal transduction; Tumors
• ISSN: 0301-4851; 1573-4978
• DOI: 10.1007/s11033-022-07655-z

Background Currently, Liver cancer is the fifth most common tumor and the second most important reason for cancer-related death in the world. However, there are still many limitations of the clinical treatment of liver cancer, and new treatment options are clearly needed. Fortunately, studies have shown that L-Selenocysteine has a certain effect on cancer. This study was to investigate the effects of L-Selenocysteine on the inhibition of cell proliferation and the promotion of apoptosis of HepG-2 cells through ROS mediated fine signaling pathway. Materials and methods CCK-8 assay was applied to evaluating the cytotoxic effect of L-Selenocysteine on HepG-2 cells. Electron microscopy, flow cytometry and Western Blot was utilization in further researching cells signaling pathways. Results The growth of HepG-2 cells was inhibited by L-selenocysteine ​​treatment in a dose-dependent manner. The cell viability decreased to 52.20%, 43.20% and 30.83% under the treatment of 4, 8, 16 µM L-selenocysteine, respectively. L-Selenocysteine had higher cytotoxicity towards HepG-2 cells than normal cells. L-Selenocysteine can induce the apoptosis of HepG-2 cells by increasing the DNA fragmentation, and activating the Caspase-3. In addition, it was found that the mechanism of the induction to HepG-2 cell apoptosis by L-Selenocysteine was closely related to the overproduction of ROS and promoted apoptosis through the Bcl-2 signaling pathway. Conclusions Our data suggest that L-selenocysteine ​​may cause mitochondrial damage and subsequently stimulate ROS production. ROS can damage cellular DNA and mediate the production of Casapase-8, Bid, Bcl-2 and other proteins, affecting downstream signaling pathways, and ultimately induced apoptosis.