1. Discovery of hydroxytyrosol as thioredoxin reductase 1 inhibitor to induce apoptosis and G1/S cell cycle arrest in human colorectal cancer cells via ROS generation
- Author
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Bing-Song Xu, Xiao-Mei Lv, Fan Wang, Ji Zhou, Yang Chen, Lei Hu, Chao Zhang, Sen-Yan Hong, Tian Wang, Sheng-Peng Zhang, Xiao-Ping Liu, Qing-Zhu Fan, and Ye-Ming Zhang
- Subjects
chemistry.chemical_classification ,Cancer Research ,Reactive oxygen species ,Cell ,Cancer ,General Medicine ,Cell cycle ,medicine.disease ,chemistry.chemical_compound ,medicine.anatomical_structure ,Immunology and Microbiology (miscellaneous) ,chemistry ,Apoptosis ,Thioredoxin Reductase 1 ,Cancer research ,medicine ,Hydroxytyrosol ,Thioredoxin - Abstract
Colorectal cancer (CRC) is one of the most common cancer types and a leading cause of cancer-associated mortality in China. Increased thioredoxin reductase 1 (TrxR1) levels have been previously identified as possible target for CRC. The present study revealed that the natural product hydroxytyrosol (HT), which exhibits a polyphenol scaffold, is a potent inhibitor of TrxR1. Inhibition of TrxR1 was indicated to result in accumulation of reactive oxygen species, inhibit proliferation and induce apoptosis and G1/S cell cycle arrest of CRC cells. Using a C-terminal mutant TrxR1 enzyme activity assay, TrxR1 RNA interference assay and HT binding model assay, the present study demonstrated the core character of the selenocysteine residue in the interaction between HT and TrxR1. HT can serve as polyphenol scaffold to develop novel TrxR1 inhibitors for CRC treatment in the future.
- Published
- 2021
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