Gold(III)-P-chirogenic complex induces mitochondrial dysfunction in triple-negative breast cancer

Area of Science:

• Oncology
• Biochemistry
• Materials Science

Background:

• Triple-negative breast cancer (TNBC) relies on oxidative phosphorylation (OXPHOS) for growth.
• Targeting metabolic vulnerabilities offers a promising therapeutic strategy for TNBC.
• Few chemical agents specifically exploit these cancer-specific metabolic pathways.

Purpose of the Study:

• To develop and characterize a novel gold(III)-based small-molecule agent, AuPhos-19.
• To investigate the selective disruption of mitochondrial metabolism in TNBC cells by AuPhos-19.
• To evaluate the anti-cancer efficacy of AuPhos-19 in vitro and in vivo.

Main Methods:

• Synthesis and characterization of the gold(III) complex AuPhos-19.
• In vitro cytotoxicity assays on murine and human TNBC cell lines and normal cells.
• Mitochondrial function assays including respiration, membrane potential, ROS production, and DNA content.
• In vivo tumor growth inhibition studies in tumor-bearing mice.

Main Results:

• AuPhos-19 demonstrated potent, selective cytotoxicity against TNBC cells (IC50 in nanomolar range).
• The compound disrupted mitochondrial respiration, induced AMPK activation, and perturbed mitochondrial function (membrane depolarization, ROS accumulation, DNA depletion).
• AuPhos-19 significantly inhibited tumor growth in a preclinical mouse model.

Conclusions:

• AuPhos-19 is a novel gold-based agent that selectively targets and disrupts mitochondrial metabolism in TNBC.
• This agent exhibits significant anti-cancer activity, highlighting its therapeutic potential.
• Targeting mitochondrial pathways with gold compounds represents a promising strategy for effective cancer treatment.