文献类型：期刊文献

英文题名：Targeting thioredoxin reductase by deoxyelephantopin from Elephantopus scaber triggers cancer cell apoptosis

作者：Duan, Dongzhu[1,2];Wang, Yanru[1,2];Pan, Dabo[3];Wang, Le[1,2];Xiao, Jian[1,2];Song, Peng[4,5];Jin, Xiaojie[6,7];Wang, Xiaoling[1,2]

第一作者：Duan, Dongzhu

通信作者：Duan, DZ[1];Wang, XL[1];Duan, DZ[2];Wang, XL[2];Song, P[3];Song, P[4]

机构：[1]Baoji Univ Arts & Sci, Shaanxi Key Lab Phytochem, Baoji 721013, Peoples R China;[2]Baoji Univ Arts & Sci, Coll Chem & Chem Engn, Baoji 721013, Peoples R China;[3]Qiandongnan Vocat & Tech Coll Nationalities, Dept Med Technol, Kaili 556000, Peoples R China;[4]Gansu Univ Chinese Med, Affiliated Hosp, Lanzhou 730000, Gansu, Peoples R China;[5]Key Lab Prevent & Treatment Chron Dis TCM, Lanzhou 730000, Gansu, Peoples R China;[6]Gansu Univ Chinese Med, Sch Pharm, Lanzhou 730000, Peoples R China;[7]Gansu Univ Chinese Med, Gansu Univ Key Lab Mol Med & Chinese Med Prevent, 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 & Chem Engn, Baoji 721013, Peoples R China;[3]corresponding author), Gansu Univ Chinese Med, Affiliated Hosp, Lanzhou 730000, Gansu, Peoples R China;[4]corresponding author), Key Lab Prevent & Treatment Chron Dis TCM, Lanzhou 730000, Gansu, Peoples R China.|[10735b845793de6ae2b30]甘肃中医药大学第二附属医院;[10735]甘肃中医药大学;

年份：2021

卷号：711

外文期刊名：ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000702565400006)】；

基金：The authors acknowledge the National Natural Science Foundation of China (82073316, 82073727, and 81803779) , the Shaanxi Provincial Key Laboratory Project (16JS009) , the Natural Science Foundation of Shaanxi province (2018JQ2051) , the Baoji University of Arts and Sci-ences (ZK16052) ; Gansu Province Science Foundation for Distinguished Young Scholars (20JR10RA348) , and the Scientific and Technological Founding of Guizhou Province (QKHZC [2020] 4Y087) .

语种：英文

外文关键词：Thioredoxin reductase; Deoxyelephantopin; Redox regulation; Oxidative stress; Apoptosis

摘要：Elevated expression of thioredoxin reductase (TrxR) is associated with the tumorigenesis and resistance to cancer chemoradiotherapy, highlighting the potential of TrxR inhibitors as anticancer drugs. Deoxyelephantopin (DET) is the major active ingredient of Elephantopus scaber and reveals potent anticancer activity. However, the potential mechanism of action and the cellular target of DET are still unknown. Here, we found that DET primarily targets the Sec residue of TrxR and irreversibly prohibits enzyme activity. Suppression of TrxR by DET leads to accumulation of reactive oxygen species and dysregulation in intracellular redox balance, eventually inducing cancer cell apoptosis mediated by oxidative stress. Noticeably, down-regulation of TrxR1 by shRNA increases cell sensitivity to DET. Collectively, targeting of TrxR1 by DET uncovers a novel mechanism of action in DET and deepens the understanding of developing DET as a potential chemotherapeutic agent for treating cancers.