A ferroptosis-inducing iridium(Ⅲ) complex

• 来源期刊: 中国科学:化学（英文版）
• 年，卷（期）: 2020,（1）
• 页码范围: 65-72
• 页数: 8页
• 语种: 英文

摘要

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.