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A Cancer Stem Cell Potent Copper(II) Complex with a S, N, S-Schiff base Ligand and Bathophenanthroline

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journal contribution
posted on 2021-09-24, 16:07 authored by J Northcote-Smith, P Kaur, K Suntharalingam
We investigate the anti-cancer stem cell (CSC) properties of two copper(II) complexes containing 4,7-diphenyl-1,10-phenanthroline and a S, N, X-Schiff base ligand, where X=O (1) or S (2). Complex 1 was previously reported by us, and is the first metal complex to induce cytotoxic and immunogenic cell death of breast CSCs. Complex 2 is a structural analogue of 1, where the phenolate moiety (within the Schiff base ligand) is replaced by a thiophenolate group. Complex 2 kills bulk breast cancer cells and breast CSCs in the sub-micromolar range, with reduced toxicity towards non-cancerous epithelial breast cells. Remarkably, 2 is over 10-fold more potent towards breast CSC spheroids than salinomycin (an established anti-breast CSC agent) and cisplatin (a clinically approved anticancer drug). Complex 2 readily enters breast CSCs, accumulates in the cytosol, and increases intracellular reactive oxygen species (ROS) levels upon short exposure (1 h). The latter is likely to be the mechanism by which 2 induces breast CSC death.

Funding

EPSRC New Investigator Award (EP/S005544/1)

History

Citation

Eur. J. Inorg. Chem. 2021, 18, (2021), 1770.

Author affiliation

School of Chemistry

Version

  • VoR (Version of Record)

Published in

European Journal of Inorganic Chemistry

Volume

2021

Issue

8

Pagination

1770 - 1775

Publisher

John Wiley & Sons, Inc

issn

1434-1948

eissn

1099-0682

Acceptance date

2021-03-15

Copyright date

2021

Available date

2021-03-15

Language

Eng

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