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 journalArticlepeer-review

10 Scopus citations

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 languageEnglish
Pages (from-to)557-565
Number of pages9
JournalChemical Science
Volume14
Issue number3
DOIs
StatePublished - Dec 12 2022

Bibliographical note

Publisher Copyright:
© 2023 The Royal Society of Chemistry

ASJC Scopus subject areas

  • General Chemistry

Fingerprint

Dive into the research topics of 'The anti-breast cancer stem cell properties of gold(i)-non-steroidal anti-inflammatory drug complexes'. Together they form a unique fingerprint.

Cite this