文献类型：期刊文献

英文题名：FDA-approved dimethyl fumarate targets thioredoxin reductase to induce apoptosis in triple-negative breast cancer

作者：Duan, Dongzhu[1,2];Pu, Yali[1,2];Wang, Yanru[1,2];Yang, Xing[1,2];Li, Mi[3,4,5];Jin, Xiaojie[3,4,5];Wang, Le[1,2];Xiao, Jian[1,2];Wang, Xiaoling[1,2];Song, Peng[1,2,3,4,5]

第一作者：Duan, Dongzhu

通信作者：Duan, DZ[1];Wang, XL[1];Song, P[1];Duan, DZ[2];Wang, XL[2];Song, P[2]

机构：[1]Baoji Univ Arts & Sci, Shaanxi Key Lab Phytochem, Baoji 721013, Peoples R China;[2]Baoji Univ Arts & Sci, Coll Chem & Mat Engn, Baoji 721013, Peoples R China;[3]Gansu Univ Chinese Med, Sch Pharm, Gansu Univ Key Lab Mol Med & Chinese Med Prevent &, Lanzhou 730000, Peoples R China;[4]Gansu Univ Chinese Med, Affiliated Hosp, Lanzhou 730000, Peoples R China;[5]Gansu Univ Chinese Med, Key Lab Prevent & Treatment Chron Dis TCM, Lanzhou 730000, Peoples R China

第一机构：Baoji Univ Arts & Sci, Shaanxi Key Lab Phytochem, Baoji 721013, Peoples R China

通信机构：[1]corresponding author), Baoji Univ Arts & Sci, Shaanxi Key Lab Phytochem, Baoji 721013, Peoples R China;[2]corresponding author), Baoji Univ Arts & Sci, Coll Chem & Mat Engn, Baoji 721013, Peoples R China.

年份：2026

卷号：256

起止页码：144

外文期刊名：FREE RADICAL BIOLOGY AND MEDICINE

收录：;Scopus(收录号：2-s2.0-105047994679);WOS:【SCI-EXPANDED(收录号:WOS:001857553000001)】；

基金：This work was supported by the Innovative Talents of Traditional Chinese Medicine Scientific Research of Shaanxi (2025-CXRC-11), the National Natural Science Foundation of China (82260859 and 82073316), the Innovation R&D Team of BUAS on Qinling Medicinal Plants and Functional Organic Molecules, the Education Department of Shaanxi Provincial Government (20JS007), Shaanxi Science and Technology Commission (2026-JC-YBMS-0162 and 2026-JC-YBMS-0180), and Gansu Province Science Foundation for Distinguished Young Scholars (20JR10RA348).

语种：英文

外文关键词：Dimethyl fumarate; Thioredoxin reductase; Drug repurposing; Oxidative stress; Apoptosis

摘要：Triple-negative breast cancer (TNBC) is characterized by poor prognosis, which is closely linked to significant tumor heterogeneity and the absence of effective targeted treatments beyond conventional chemotherapy, thereby necessitating the discovery of novel therapeutic options. Altered thioredoxin reductase (TrxR) activity is tightly associated with tumorigenesis and cancer progression, positioning TrxR as a promising target for anticancer intervention. Dimethyl fumarate (DMF), an FDA-approved drug for treatment of psoriasis and multiple sclerosis, has also demonstrated direct antitumor activity in several cancers. Although DMF exhibits significant antitumor effects in TNBC xenograft models, the molecular mechanism underlying its action on TrxR remains to be fully elucidated. Here we show that DMF selectively inhibits TrxR activity by targeting the selenocysteine 498 residue. Pharmacological suppression of TrxR activity by DMF promoted ROS accumulation and disrupted intracellular redox homeostasis, ultimately triggering apoptosis in tumor cells through oxidative stress. Furthermore, the interaction of DMF with GSH may disrupt intracellular thiol balance, thereby reinforcing the apoptotic response elicited in TNBC cells. Interestingly, DMF treatment inhibited tumor growth in vivo. Collectively, these findings identify DMF as a novel TrxR inhibitor that induces redox imbalance and apoptosis in TNBC, highlighting its potential as a repurposed therapeutic agent for this aggressive breast cancer subtype.