A copper(II) phenanthroline metallopeptide that targets and disrupts mitochondrial function in breast cancer stem cells
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Kristine Laws Ganka Bineva-Todd Arvin Eskandari Chunxin Lu Nicola O'Reilly Kogularamanan SuntharalingamAbstract
The breast cancer stem cell (CSC) and bulk breast cancer cell potency of a series of metallopeptides containing dichloro(1,10-phenanthroline)copper(II) and various organelle-targeting peptide sequences is reported. The mitochondria-targeting metallopeptide 1 exploits the higher mitochondrial load in breast CSCs over the corresponding non-CSCs and the vulnerability of breast CSCs to mitochondrial damage to potently and selectively kill breast CSCs. Strikingly, 1 reduces the formation and size of mammospheres to a greater extent than salinomycin, an established CSC-potent agent. Mechanistic studies show that 1 enters CSC mitochondria, induces mitochondrial dysfunction, generates reactive oxygen species (ROS), activates JNK and p38 pathways, and prompts apoptosis. To the best of our knowledge, 1 is the first metallopeptide to selectivity kill breast CSCs in vitro.
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Volume 57
Issue number 1
Pages 287-291
Available online
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Publisher website (DOI) 10.1002/anie.201710910
Europe PubMed Central 29144008
Pubmed 29144008
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