Open Access

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

  • Authors:
    • Sheng-Peng Zhang
    • Ji Zhou
    • Qing-Zhu Fan
    • Xiao-Mei Lv
    • Tian Wang
    • Fan Wang
    • Yang Chen
    • Sen-Yan Hong
    • Xiao-Ping Liu
    • Bing-Song Xu
    • Lei Hu
    • Chao Zhang
    • Ye-Ming Zhang
  • View Affiliations

  • Published online on: June 3, 2021     https://doi.org/10.3892/etm.2021.10261
  • Article Number: 829
  • Copyright: © Zhang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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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.
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August-2021
Volume 22 Issue 2

Print ISSN: 1792-0981
Online ISSN:1792-1015

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Copy and paste a formatted citation
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Spandidos Publications style
Zhang S, Zhou J, Fan Q, Lv X, Wang T, Wang F, Chen Y, Hong S, Liu X, Xu B, Xu B, et al: 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. Exp Ther Med 22: 829, 2021.
APA
Zhang, S., Zhou, J., Fan, Q., Lv, X., Wang, T., Wang, F. ... Zhang, Y. (2021). 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. Experimental and Therapeutic Medicine, 22, 829. https://doi.org/10.3892/etm.2021.10261
MLA
Zhang, S., Zhou, J., Fan, Q., Lv, X., Wang, T., Wang, F., Chen, Y., Hong, S., Liu, X., Xu, B., Hu, L., Zhang, C., Zhang, Y."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". Experimental and Therapeutic Medicine 22.2 (2021): 829.
Chicago
Zhang, S., Zhou, J., Fan, Q., Lv, X., Wang, T., Wang, F., Chen, Y., Hong, S., Liu, X., Xu, B., Hu, L., Zhang, C., Zhang, Y."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". Experimental and Therapeutic Medicine 22, no. 2 (2021): 829. https://doi.org/10.3892/etm.2021.10261