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.