PT  - JOURNAL ARTICLE
AU  - Han, Xiao
AU  - Zhang, Junmin
AU  - Shi, Danfeng
AU  - Wu, Yueting
AU  - Liu, Ruijuan
AU  - Liu, Tianyu
AU  - Xu, Jianqiang
AU  - Yao, Xiaojun
AU  - Fang, Jianguo
TI  - Targeting Thioredoxin Reductase by Ibrutinib Promotes Apoptosis of SMMC-7721 Cells
AID  - 10.1124/jpet.118.254862
DP  - 2019 May 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 212--222
VI  - 369
IP  - 2
4099  - http://jpet.aspetjournals.org/content/369/2/212.short
4100  - http://jpet.aspetjournals.org/content/369/2/212.full
SO  - J Pharmacol Exp Ther2019 May 01; 369
AB  - Ibrutinib (IBT), the first-in-class inhibitor of Bruton’s tyrosine kinase (BTK), has demonstrated clinical activity against various B-cell malignancies. Aside from its therapeutic mechanism through BTK inhibition, IBT has other target sites reported for cancer therapy, leading us to investigate whether IBT has unreported targets. Our study revealed that IBT can inhibit SMMC-7721 cells through irreversible inhibition of mammalian thioredoxin reductase enzymes. Further study demonstrated that IBT can cause cellular reactive oxygen species elevation and induce cancer cell apoptosis. The discovery of a new target of IBT sheds light on better understanding its anticancer mechanisms and provides a theoretical foundation for its further use in clinical therapy.