A Copper(II) Phenanthroline Metallopeptide That Targets and Disrupts Mitochondrial Function in Breast Cancer Stem Cells

Kristine Laws, Ganka Bineva-Todd, Arvin Eskandari, Chunxin Lu, Nicola O'Reilly, Kogularamanan Suntharalingam*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

84 Citations (Scopus)

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 invitro.

Original languageEnglish
Pages (from-to)287-291
JournalANGEWANDTE CHEMIE-INTERNATIONAL EDITION
Volume57
Issue number1
Early online date16 Nov 2017
DOIs
Publication statusPublished - 2 Jan 2018

Keywords

  • Antitumor agents
  • Cancer
  • Copper
  • Metallopeptides
  • Mitochondria

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