文献类型：期刊文献

英文题名：Natural diterpenoid eriocalyxin B covalently modifies glutathione and selectively inhibits thioredoxin reductase inducing potent oxidative stress-mediated apoptosis in colorectal carcinoma RKO cells

作者：Duan, Dongzhu[1,2];Wang, Yanru[1,2];Jin, Xiaojie[3,4];Li, Mi[3,4];Wang, Le[1,2];Yan, Yunyun[1,2];Xiao, Jian[1,2];Song, Peng[5,6];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]Gansu Univ Chinese Med, Sch Pharm, Lanzhou 730000, Peoples R China;[4]Gansu Univ Chinese Med, Gansu Univ Key Lab Mol Med & Chinese Med Prevent, Lanzhou 730000, Peoples R China;[5]Gansu Univ Chinese Med, Affiliated Hosp, Lanzhou 730000, Gansu, Peoples R China;[6]Key Lab Prevent & Treatment Chron Dis TCM, Lanzhou 730000, Gansu, 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：177

起止页码：15

外文期刊名：FREE RADICAL BIOLOGY AND MEDICINE

收录：;Scopus(收录号：2-s2.0-85118722660);WOS:【SCI-EXPANDED(收录号:WOS:000710699100002)】；

基金：This work was supported by the National Natural Science Foundation of China (82073727, 82073316, and 81803779) , the Natural Science Foundation of Shaanxi province (2018JQ2051) , the Shaanxi Provincial Key Laboratory Project (16JS009 and 17JS010) , Gansu Province Science Foundation for Distinguished Young Scholars (20JR10RA348) , and the Baoji University of Arts and Sciences (ZK16052) .

语种：英文

外文关键词：Thioredoxin reductase; Eriocalyxin B; Colorectal cancer; Redox homeostasis; Oxidative stress; Apoptosis

摘要：Increasing evidence suggests the significant contribution of high levels of thioredoxin reductase (TrxR) in various stages of tumorigenesis and resistance to tumor chemotherapy. Thus, inhibition of TrxR with small molecules is an attractive strategy for cancer therapy. Eriocalyxin B (EriB), a naturally occurring diterpenoid extracted from Isodon eriocalyx, has reflected potential anticancer activities through numerous pathways. Here, we describe that EriB covalently modifies GSH and selectively inhibits TrxR activity by targeting the Sec residue of the enzyme. Pharmacological inhibition of TrxR by EriB results in elevated ROS levels, reduced total GSH and thiols content, which ultimately induced potent RKO cell apoptosis mediated by oxidative stress. Importantly, EriB indicates potent synthetic lethality with GSH inhibitors, BSO, in RKO cells. In summary, our results highlight that targeting TrxR by EriB explores a novel mechanism for the biological action of EriB. This opened up a new therapeutic indication for using EriB to combat cancers.