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Immunogenic Cell Death of Breast Cancer Stem Cells by an Endoplasmic Reticulum-Targeting Copper(II) Complex.

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journal contribution
posted on 17.09.2020, 13:59 by Pooja Kaur, Alice Johnson, Joshua Northcote-Smith, Chunxin Lu, Kogularamanan Suntharalingam
Immunogenic cell death (ICD) offers a method of stimulating the immune system to attack and remove cancer cells. We report a copper(II) complex containing a Schiff base ligand and a polypyridyl ligand, 4 capable of inducing ICD in breast cancer stem cells (CSCs). The complex, 4 kills both bulk breast cancer cells and breast CSCs in the sub-micromolar range. Notably, 4 exhibits greater potency (one order of magnitude) towards breast CSCs than salinomycin (an established breast CSC-potent agent) and cisplatin (a clinically approved anticancer drug). Epithelial spheroid studies show that 4 is able to selectively inhibit breast CSC-enriched HMLER-shEcad spheroid formation and viability over non-tumorigenic breast MCF10A spheroids. Mechanistic studies show that 4 operates as a Type II ICD inducer. Specifically, 4 readily enters the endoplasmic reticulum (ER) of breast CSCs, elevates intracellular reactive oxygen species (ROS) levels, induces ER stress, evokes damage-associated molecular patterns (DAMPs), and promotes breast CSC phagocytosis by macrophages. As far as we are aware, 4 is the first metal complex to induce ICD in breast CSCs and promote their engulfment by immune cells.

History

Citation

ChemBioChem 10.1002/cbic.202000553

Author affiliation

School of Chemistry

Version

AM (Accepted Manuscript)

Published in

Chembiochem : a European journal of chemical biology

Publisher

Wiley

issn

1439-4227

eissn

1439-7633

Acceptance date

09/08/2020

Copyright date

2020

Available date

09/08/2021

Spatial coverage

Germany

Language

eng

Publisher version

https://chemistry-europe.onlinelibrary.wiley.com/doi/abs/10.1002/cbic.202000553