文献类型：期刊文献

英文题名：Rheumatoid arthritis drug sinomenine induces apoptosis of cervical tumor cells by targeting thioredoxin reductase in vitro and in vivo

作者：Duan, Dongzhu[1,2];Wang, Yanru[1,2];Pan, Dabo[4];Jin, Xiaojie[5,6];Yan, Yunyun[1,2];Song, Peng[7,8];Wang, Le[1,2];Xiao, Jian[1,2];Wang, Zihua[3];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];Wang, ZH[3]

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]Fujian Med Univ, Sch Basic Med Sci, Fujian Prov Key Lab Brain Aging & Neurodegenerat, Fuzhou 350122, Peoples R China;[4]Qiandongnan Vocat & Tech Coll Nationalities, Dept Med Technol, Kaili 556000, Peoples R China;[5]Gansu Univ Chinese Med, Sch Pharm, Lanzhou 730000, Peoples R China;[6]Gansu Univ Chinese Med, Gansu Univ Key Lab Mol Med & Chinese Med Prevent, Lanzhou 730000, Peoples R China;[7]Gansu Univ Chinese Med, Affiliated Hosp, Lanzhou 730000, Gansu, Peoples R China;[8]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), Fujian Med Univ, Sch Basic Med Sci, Fujian Prov Key Lab Brain Aging & Neurodegenerat, Fuzhou 350122, Peoples R China.

年份：2022

卷号：122

外文期刊名：BIOORGANIC CHEMISTRY

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000820482100007)】；

基金：This work was supported by the National Natural Science Foundation of China (82073316, 82073727, and 81803779), the Shaanxi Provincial Key Laboratory Project (17JS010), the Natural Science Foundation of Shaanxi province (2018JQ2074 and 2022TD-63), the Baoji University of Arts and Sciences (ZK16052); Gansu Province Science Foundation for Distinguished Young Scholars (20JR10RA348), the Scientific and Technological Founding of Guizhou Province (QKHZC[2020]4Y087), and the Joint Funds for the Innovation of Science and Technology Fujian Province (2019Y9001).

语种：英文

外文关键词：Sinomenine; Thioredoxin reductase; Chemotherapeutic agents; Reactive oxygen species; Oxidative stress; Apoptosis

摘要：Overexpression of thioredoxin reductase (TrxR) has been linked to tumorigenesis and phenotypic maintenance of malignant tumors. Thus, targeting TrxR with natural molecules is a promising strategy for developing anticancer drugs. Sinomenine is a naturally occurring alkaloid isolated from Sinomenium acutum. The drug, Zhengqing Fengtongning made from sinomenine, has been universally applied in rheumatoid arthritis treatment in China as well as other Asian countries for decades. Recently, increasing evidence indicates that sinomenine appears to be a promising therapeutic agent against various cancer cells. However, the exact mechanism underlying the anticancer activity of sinomenine remains unclear. In this study, we identified sinomenine as a kind of new inhibitor for TrxR. Pharmacological inhibition of TrxR by sinomenine results in the decrease of thiols content, increases the levels of reactive oxygen species, and finally facilitates oxidative stress-mediated cancer cell apoptosis. It is vital that knockdown in TrxR1 by shRNA can increase cell sensitivity to sinomenine. Treatment with sinomenine in vivo leads to a decrease in TrxR activity and tumor growth, and an increase in apoptosis. Our findings provide a novel action mechanism related to sinomenine and presents an insight on how to develop sinomenine as a chemotherapeutic agent for cancer therapy.