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Interaction of glaucocalyxin a with glutathione and thioredoxin reductase for triple-negative breast cancer treatment  ( SCI-EXPANDED收录)  

文献类型:期刊文献

英文题名:Interaction of glaucocalyxin a with glutathione and thioredoxin reductase for triple-negative breast cancer treatment

作者:Duan, Dongzhu[1,2];Yang, Xing[1,2];Guo, Xiangyu[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[3,4,5]

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];Song, P[5]

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, Gansu Univ Chinese Med, Sch Pharm, Key Lab Mol Med & Chinese Med Prevent & Treatment, 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 & Chem Engn, Baoji 721013, Peoples R China;[3]corresponding author), Gansu Univ, Gansu Univ Chinese Med, Sch Pharm, Key Lab Mol Med & Chinese Med Prevent & Treatment, Lanzhou 730000, Peoples R China;[4]corresponding author), Gansu Univ Chinese Med, Affiliated Hosp, Lanzhou 730000, Peoples R China;[5]corresponding author), Gansu Univ Chinese Med, Key Lab Prevent & Treatment Chron Dis TCM, Lanzhou 730000, Peoples R China.|[10735]甘肃中医药大学;[10735b845793de6ae2b30]甘肃中医药大学第二附属医院;

年份:2025

卷号:161

外文期刊名:BIOORGANIC CHEMISTRY

收录:;Scopus(收录号:2-s2.0-105004675899);WOS:【SCI-EXPANDED(收录号:WOS:001491297600003)】;

基金:This work was supported by the National Natural Science Foundation of China (82073316, 82073727, and 82260859), the Innovation Capability Support Program of Shaanxi (2022TD-63), 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 (2023-JC-YB-659), and Gansu Province Science Foundation for Distinguished Young Scholars (20JR10RA348).

语种:英文

外文关键词:Thioredoxin reductase; Glaucocalyxin a; Triple-negative breast cancer; Oxidative stress; Apoptosis

摘要:Glaucocalyxin A (GLA) is a bioactive diterpenoid isolated from Rabdosia japonica var. that has been applied for centuries in traditional Chinese medicine. Although GLA exhibits potent anticancer activity against various human cancer cells, its cellular targets remain largely unidentified. We reported here that GLA covalently modifies glutathione and selectively inhibits TrxR activity by primarily targeting the Sec498 residue of the protein. Pharmacologic inhibition of TrxR with GLA results in accumulation of reactive oxygen species, decreased total glutathione and thiols, collapse of the intracellular redox balance, and eventually induction of oxidative stress mediated apoptosis in triple-negative breast cancer cells. Importantly, knockdown of TrxR1 increases the sensitivity cells to GLA. Targeting TrxR by GLA thus discloses a newly identified molecular mechanism underlying the biological activity of GLA, and provides an in-depth insight in understanding the action of GLA in treatment of cancer.

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