Title of Paper:Targeting Thioredoxin Reductase by Ibrutinib Promotes Apoptosis of SMMC-7721 Cells

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Date of Publication:2019-05-01

Journal:The Journal of pharmacology and experimental therapeutics

Included Journals:PubMed

Volume:369

Issue:2

Page Number:212-222

ISSN No.:1521-0103

Key Words:cell death,drug targeting,molecular drug targeting

Abstract: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.Copyright © 2019 by The American Society for Pharmacology and Experimental Therapeutics.