The Anti-breast Cancer Stem Cell Properties of Gold(i)-non-steroidal Anti-inflammatory Drug Complexes

Overview

Journal Chem Sci

Publisher Royal Society of Chemistry

Specialty Chemistry

Date 2023 Feb 6

PMID 36741517

Authors

Alice Johnson

Chibuzor Olelewe

Jong Hyun Kim

Joshua Northcote-Smith

R Tyler Mertens

Ginevra Passeri

Kuldip Singh

Samuel G Awuah

Kogularamanan Suntharalingam

Affiliations

Soon will be listed here.

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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