文献类型：期刊文献

英文题名：Sanguinarine as a new chemical entity of thioredoxin reductase inhibitor to elicit oxidative stress and promote tumor cell apoptosis

作者：Yao, Juan[1,2,3];Duan, Dongzhu[1,2,4];Song, Zi-Long[1,2];Zhang, Junmin[1,2];Fang, Jianguo[1,2]

第一作者：Yao, Juan;姚娟

通信作者：Fang, JG[1];Fang, JG[2]

机构：[1]Lanzhou Univ, State Key Lab Appl Organ Chem, Lanzhou 730000, Gansu, Peoples R China;[2]Lanzhou Univ, Coll Chem & Chem Engn, Lanzhou 730000, Gansu, Peoples R China;[3]Gansu Univ Chinese Med, Sch Pharm, Lanzhou 730000, Gansu, Peoples R China;[4]Baoji Univ Arts & Sci, Shaanxi Key Lab Phytochem, Baoji 721013, Peoples R China

第一机构：Lanzhou Univ, State Key Lab Appl Organ Chem, Lanzhou 730000, Gansu, Peoples R China

通信机构：[1]corresponding author), Lanzhou Univ, State Key Lab Appl Organ Chem, Lanzhou 730000, Gansu, Peoples R China;[2]corresponding author), Lanzhou Univ, Coll Chem & Chem Engn, Lanzhou 730000, Gansu, Peoples R China.

年份：2020

卷号：152

起止页码：659

外文期刊名：FREE RADICAL BIOLOGY AND MEDICINE

收录：;Scopus(收录号：2-s2.0-85077915168);WOS:【SCI-EXPANDED(收录号:WOS:000542949900010)】；

基金：The financial supports from the National Natural Science Foundation of China (21778028 & 21572093), the 111 project and the Natural Science Foundation of Gansu Province (18JR4RA003) are greatly acknowledged. The authors also express heartfelt appreciation to Prof. Arne Holmgren for recombinant rat TrxR1, and to Prof. Constantinos Koumenis for HEK-TrxR1 and HEK-IRES cells. The authors confirm that there are no conflicts of interest.

语种：英文

外文关键词：Thioredoxin; Sanguinarine; Phenanthridinium; Oxidative stress; Apoptosis

摘要：The alteration of redox homeostasis is a hallmark of cancer cells. As a critical player in regulating cellular redox signaling, thioredoxin reductase (TrxR) enzymes are increasingly recognized as attractive targets for anticancer drug development. We reported herein the natural product sanguinarine (SAN) as a potent inhibitor of TrxR with a new chemical sca ffold. Inhibition of TrxR leads to accumulation of the oxidized thioredoxin, elicits oxidative stress, and finally promotes apoptosis of cancer cells. Further synthesis of di fferent model compounds of SAN demonstrated that the phenanthridinium unit is responsible for the TrxR inhibition. The core structure of SAN, e.g., the phenanthridinium moiety, is di fferent from those of known TrxR inhibitors, and thus SAN is a new chemical entity of TrxR inhibitors and may serve a lead for further development. In addition, as the phenan- thridinium sca ffold is widely present in natural products, the disclosure of TrxR inhibition by such unit sheds light in understanding the pharmacological actions of these molecules.