Citation: Shuangshuang GAI, Jixiang CAI, Moya YANG, Haijuan WU, Shuzhen FENG, Ming JIANG. Endoplasmic reticulum stress and mitochondrial apoptosis in thiosemicarbazone copper(Ⅱ) complex-triggered triple-negative breast cancer cell death[J]. Chinese Journal of Inorganic Chemistry, ;2026, 42(5): 1073-1084. doi: 10.11862/CJIC.20250328 shu

Endoplasmic reticulum stress and mitochondrial apoptosis in thiosemicarbazone copper(Ⅱ) complex-triggered triple-negative breast cancer cell death

Shuangshuang GAI ^{1, #} ,
Jixiang CAI ^{1, #} ,
Moya YANG ¹ ,
Haijuan WU ¹ ,
Shuzhen FENG ^2,, ,
Ming JIANG ^1,,

1.
Guangxi Key Laboratory of Green Preparation and Application of Inorganic Materials, Guangxi Science & Technology Normal University, Laibin, Guangxi 546199, China
2.
Medical College, Guangxi University of Science and Technology, Liuzhou, Guangxi 545616, China

Corresponding author: Shuzhen FENG, fengshuzhen@gxust.edu.cn Ming JIANG, jiangbiochem@163.com
Received Date: 28 October 2025
Revised Date: 22 January 2026

Figures(9)

To investigate the antitumor properties of copper(Ⅱ) complexes, a series of Cu(Ⅱ) complexes (C1-C3) derived from 6, 7-dihydro-5H-quinoline-8-one thiosemicarbazone ligands was designed and synthesized. These complexes exhibited significantly higher potency in inhibiting tumor cell growth in vitro compared to cisplatin. Among them, C3 had the highest antitumor activity against MDA-MB-231 cells, with a half maximal inhibitory concentration (IC₅₀) value of 1.42 μmol·L^-1. Moreover, C3 effectively inhibited the growth of 3D multicellular spheres. Mechanistically, it induced significant reactive oxygen species (ROS) generation, initiating a dual-pathway cytotoxic effect. On the one hand, it triggers endoplasmic reticulum stress and inhibits the activity of the related protein, protein disulfide isomerase (PDI). On the other hand, it induces mitochondrial dysfunction. These combined stresses ultimately lead to the apoptosis of MDA-MB-231 cells.
- anticancer,
- triple-negative breast cancer,
- Cu(Ⅱ) complex,
- thiosemicarbazone,
- protein disulfide isomerase
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沈阳化工大学材料科学与工程学院沈阳 110142