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

Alice Johnson; Chibuzor Olelewe; Jong Hyun Kim; Joshua Northcote-Smith; R. Tyler Mertens; Ginevra Passeri; Kuldip Singh; Samuel G. Awuah; Kogularamanan Suntharalingam

doi:10.1039/d2sc04707a

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

Alice Johnson, Chibuzor Olelewe, Jong Hyun Kim, Joshua Northcote-Smith, R. Tyler Mertens, Ginevra Passeri, Kuldip Singh, Samuel G. Awuah, Kogularamanan Suntharalingam

Research output: Contribution to journal › Article › peer-review

Abstract

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.

Original language	English
Pages (from-to)	557-565
Number of pages	9
Journal	Chemical Science
Volume	14
Issue number	3
DOIs	https://doi.org/10.1039/d2sc04707a
State	Published - Dec 12 2022

Bibliographical note

Funding Information:
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.

Publisher Copyright:
© 2023 The Royal Society of Chemistry

ASJC Scopus subject areas

Chemistry (all)

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1039/d2sc04707a

Cite this

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

abstract = "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.",

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note = "Funding Information: 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. Publisher Copyright: {\textcopyright} 2023 The Royal Society of Chemistry",

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

Abstract

Bibliographical note

ASJC Scopus subject areas

UN SDGs

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