Journal
SCIENCE CHINA-CHEMISTRY
Volume 63, Issue 1, Pages 65-72Publisher
SCIENCE PRESS
DOI: 10.1007/s11426-019-9577-3
Keywords
iridium; proteome; ferroptosis; heme oxygenase 1
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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.
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