A gold-based inhibitor of oxidative phosphorylation is effective against triple negative breast cancer

Abstract

Triple-negative breast cancer (TNBC) is associated with metabolic heterogeneity and poor prognosis with limited treatment options. New treatment paradigms for TNBC remains an unmet need. Thus, therapeutics that target metabolism are particularly attractive approaches. We previously designed organometallic Au(III) compounds capable of modulating mitochondrial respiration by ligand tuning with high anticancer potency in vitro and in vivo. Here, we show that an efficacious Au(III) dithiocarbamate (AuDTC) compound induce mitochondrial dysfunction and oxidative damage in cancer cells. Efficacy of AuDTC in TNBC mouse models harboring mitochondrial oxidative phosphorylation (OXPHOS) dependence and metabolic heterogeneity establishes its therapeutic potential following systemic delivery. This provides evidence that AuDTC is an effective modulator of mitochondrial respiration worthy of clinical development in the context of TNBC. One sentence summary: Metabolic-targeting of triple-negative breast cancer by gold anticancer agent may provide efficacious therapy.

Publisher

Elsevier France-Editions Scientifiques Medicales

Publication Date

1-1-2024

Publication Title

Biomedicine & Pharmacotherapy

Department

Neuroscience

Document Type

Article

DOI

https://dx.doi.org/10.1016/j.biopha.2023.116010

Keywords

Gold, Mitochondria, Triple negative breast cancer

Language

English

Format

text

Link to Full Text

Share

COinS