The anti-breast cancer stem cell properties of gold( i )-non-steroidal anti-inflammatory drug complexes

JOHNSON, Alice, OLELEWE, Chibuzor, KIM, Jong Hyun, NORTHCOTE-SMITH, Joshua, MERTENS, R. Tyler, PASSERI, Ginevra, SINGH, Kuldip, AWUAH, Samuel G. and SUNTHARALINGAM, Kogularamanan (2022). The anti-breast cancer stem cell properties of gold( i )-non-steroidal anti-inflammatory drug complexes. Chemical Science.

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The anti-breast cancer stem cell (CSC) properties of a series of gold(i) complexes comprising various non-steroidal anti-inflammatory drugs (NSAIDs) and triphenylphosphine 1–8 are reported. The most effective gold(i)-NSAID complex 1, containing indomethacin, exhibits greater potency for breast CSCs than bulk breast cancer cells (up to 80-fold). Furthermore, 1 reduces mammosphere viability to a better extent than a panel of clinically used breast cancer drugs and salinomycin, an established anti-breast CSC agent. Mechanistic studies suggest 1-induced breast CSC death results from breast CSC entry, cytoplasm localisation, an increase in intracellular reactive oxygen species levels, cyclooxygenase-2 downregulation and inhibition, and apoptosis. Remarkably, 1 also significantly inhibits tumour growth in a murine metastatic triple-negative breast cancer model. To the best of our knowledge, 1 is the first gold complex of any geometry or oxidation state to demonstrate anti-breast CSC properties.

Item Type: Article
Additional Information: ** Embargo end date: 12-12-2022 ** From Royal Society of Chemistry via Jisc Publications Router ** Licence for this article starting on 12-12-2022: ** Acknowledgements: K. S. is supported by an EPSRC New Investigator Award (EP/S005544/1) and the University of Leicester. XRD crystallography at the University of Leicester is supported by an EPSRC Core Equipment Award (EP/V034766/1). We thank Dr Fabrizio Ortu for advice and assistance with presenting the XRD data. S. G. A. thanks the University of Kentucky and the National Institutes of Health/NCI (R01CA258421-01) for funding. **Journal IDs: pissn 2041-6520; eissn 2041-6539 **Article IDs: publisher-id: d2sc04707a **History: published 12-12-2022; accepted 10-12-2022; submitted 23-08-2022
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SWORD Depositor: Colin Knott
Depositing User: Colin Knott
Date Deposited: 22 Dec 2022 12:41
Last Modified: 12 Oct 2023 08:30

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