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The Anti-Breast Cancer Stem Cell Potency of Copper(I)-Non-Steroidal Anti-Inflammatory Drug Complexes

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posted on 2024-02-27, 09:55 authored by A Johnson, X Feng, K Singh, Fabrizio OrtuFabrizio Ortu, K Suntharalingam

Cancer stem cells (CSCs) are thought to be partly responsible for metastasis and cancer relapse. Currently, there are no effective therapeutic options that can remove CSCs at clinically safe doses. Here, we report the synthesis, characterisation, and anti-breast CSC properties of a series of copper(I) complexes, comprising of non-steroidal anti-inflammatory drugs (NSAIDs) and triphenylphosphine ligands (1–3). The copper(I) complexes are able to reduce the viability of breast CSCs grown in two- and three-dimensional cultures at micromolar concentrations. The potency of the copper(I) complexes towards breast CSCs was similar to salinomycin (an established anti-breast CSC agent) and cisplatin (a clinically used metallopharmaceutical). Cell-based studies showed that the copper(I) complexes are readily, and similarly, internalised by breast CSCs. The copper(I) complexes significantly increase the intracellular reactive oxygen species (ROS) levels in breast CSCs, and their ROS generation profile with respect to time is dependent on the NSAID component present. The generation of intracellular ROS by the copper(I) complexes could be part of the underlying mechanism by which they evoke breast CSC death. As far as we are aware, this is the first study to explore the anti-breast CSC properties of copper(I) complexes.

Funding

Immuno-chemotherapeutic Metal Complexes for Cancer Stem Cell-Directed Therapy

Engineering and Physical Sciences Research Council

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SubVAR - Sub-Valent Alkaline Earth Reagents

Engineering and Physical Sciences Research Council

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Single crystal X-ray diffractometer

Engineering and Physical Sciences Research Council

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University of Leicester

History

Author affiliation

College of Science & Engineering/Chemistry

Version

  • VoR (Version of Record)

Published in

Molecules

Volume

28

Issue

17

Pagination

6401

Publisher

MDPI AG

issn

1420-3049

eissn

1420-3049

Copyright date

2023

Available date

2024-02-27

Spatial coverage

Switzerland

Language

eng

Deposited by

Dr Fabrizio Ortu

Deposit date

2024-02-12

Rights Retention Statement

  • No

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