We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
A Copper(II) Phenanthroline Metallopeptide That Targets and Disrupts Mitochondrial Function in Breast Cancer Stem Cells.
- Authors
Laws, Kristine; Bineva‐Todd, Ganka; Eskandari, Arvin; Lu, Chunxin; O'Reilly, Nicola; Suntharalingam, Kogularamanan
- Abstract
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.
- Subjects
COPPER compounds synthesis; CANCER stem cells; C-Jun N-terminal kinases; AMINO acid sequence; SALINOMYCIN; BREAST cancer treatment; MITOCHONDRIAL physiology
- Publication
Angewandte Chemie, 2018, Vol 130, Issue 1, p293
- ISSN
0044-8249
- Publication type
Article
- DOI
10.1002/ange.201710910