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

Abstract

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.

• Authors: Kaiying Zhang, Jingyao Su, Danyang Chen, Binger Lin, Yucan Wu, Yibing Wang, Jiapei Lei, Ruilin Zheng, Bing Zhu, Yinghua Li
• Journal: Molecular biology reports (Mol Biol Rep) Vol. 49 Issue 9 Pg. 8381-8390 (Sep 2022) ISSN: 1573-4978 [Electronic] Netherlands
• PMID: 35716289 (Publication Type: Journal Article)
• Copyright: © 2022. The Author(s), under exclusive licence to Springer Nature B.V.

Chemical References

• Proto-Oncogene Proteins c-bcl-2
• Reactive Oxygen Species
• Selenocysteine

Topics

• Apoptosis
• Cell Line, Tumor
• Humans
• Liver Neoplasms (metabolism)
• Membrane Potential, Mitochondrial
• Mitochondria (metabolism)
• Proto-Oncogene Proteins c-bcl-2 (genetics)
• Reactive Oxygen Species (metabolism)
• Selenocysteine (metabolism, pharmacology, therapeutic use)
• Signal Transduction