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

xlomafota13 shared this article with you from Inoreader Discovery of hydroxytyrosol as thioredoxin reductase 1 inhibitor to induce apoptosis and G<sub>1</sub>/S cell cycle arrest in human colorectal cancer cells via ROS generation Via Experimental and therapeutic medicine Exp Ther Med. 2021 Aug;22(2):829. doi: 10.3892/etm.2021.10261. Epub 2021 Jun 3. 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 inhibitor s for CRC treatment in the future. PMID:34149875 | PMC:PMC8200807 | DOI:10.3892/etm.2021.10261 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.