2. Academic Validation
  3. 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

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

  • Exp Ther Med. 2021 Aug;22(2):829. doi: 10.3892/etm.2021.10261.
Sheng-Peng Zhang 1,  Ji Zhou 2,  Qing-Zhu Fan 1,  Xiao-Mei Lv 1,  Tian Wang 3,  Fan Wang 3,  Yang Chen 3,  Sen-Yan Hong 3,  Xiao-Ping Liu 1,  Bing-Song Xu 3,  Lei Hu 3,  Chao Zhang 1,  Ye-Ming Zhang 3
Affiliations

Affiliations

  • 1 Center of Drug Screening and Evaluation, Wannan Medical College, Wuhu, Anhui 241000, P.R. China.
  • 2 Center for Reproductive Medicine, The First Affiliated Hospital, Wannan Medical College, Wuhu, Anhui 241000, P.R. China.
  • 3 School of Pharmacy, Wannan Medical College, Wuhu, Anhui 241000, P.R. China.
PMID: 34149875 DOI: 10.3892/etm.2021.10261
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.

Keywords

antitumor; apoptosis; hydroxytyrosol; oxidative stress; thioredoxin.

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