A ferroptosis-inducing iridium(III) complex

Ferroptosis is a recently emerging non-apoptotic mode of cell death involving the production of iron-dependent reactive oxygen species (ROS). Here we described a mitochondria-targeted iridium (III) complex IrFN that exhibited potent antiproliferative activity against a variety of cancer cells, espec...

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Bibliographic Details
Published in:Science China. Chemistry 2020, Vol.63 (1), p.65-72
Main Authors: Wang, Xiuxiu, Chen, Feng, Zhang, Jingyi, Sun, Jianxuan, Zhao, Xinyang, Zhu, Yuelu, Wei, Wei, Zhao, Jing, Guo, Zijian
Format: Article
Language:English
Subjects:
Cell death
Chemistry
Chemistry and Materials Science
Chemistry/Food Science
Chromatography
Cytotoxicity
Ferroptosis
Gene expression
Homeostasis
Iridium compounds
Iron
Ligands
Lipid peroxidation
Lipids
Lung cancer
Mitochondria
Ovarian cancer
Polypeptides
Proteins
Proteomics
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Summary:Ferroptosis is a recently emerging non-apoptotic mode of cell death involving the production of iron-dependent reactive oxygen species (ROS). Here we described a mitochondria-targeted iridium (III) complex IrFN that exhibited potent antiproliferative activity against a variety of cancer cells, especially the A2780 human ovarian cancer cells, through the ferroptosis pathways. Mechanistic studies by label-free quantitative proteomics profiling indicated that heme oxygenase 1 (HMOX1)-mediated ferroptosis process was activated by IrFN. The study on iron-dependent cell death, ROS accumulation, lipid peroxidation, and over released iron further confirmed the ferroptosis processes. mRNA transcription quantification, in vitro over-expression of HMOX1, and RNAi-mediated knock-down experiments suggested that IrFN activated the over-expression of HMOX1. Our report revealed the first case of anticancer iridium complex leading to ferroptosis, highlighting ferroptosis as a promising approach in future design of metallodrugs.
ISSN:1674-7291
1869-1870
DOI:10.1007/s11426-019-9577-3