Ergosterol Peroxide Disrupts Triple-Negative Breast Cancer Mitochondrial Function and Inhibits Tumor Growth and...

Area of Science:

• Biochemistry
• Molecular Biology
• Oncology

Background:

• Triple-negative breast cancer (TNBC) is an aggressive subtype with limited therapeutic options.
• Ergosterol peroxide (EP) is known to induce apoptosis via reactive oxygen species (ROS) in TNBC cells.
• Mitochondrial dysfunction is implicated in cancer progression and may be a target for EP therapy.

Purpose of the Study:

• To investigate the mechanism by which EP induces apoptosis in TNBC cells, focusing on ROS-induced mitochondrial dysfunction.
• To assess the impact of EP on mitochondrial membrane potential (MMP), cellular respiration, and glycolysis in TNBC models.
• To evaluate the in vivo efficacy of EP in reducing tumor volume and metastasis in TNBC models.

Main Methods:

• Assays to measure mitochondrial membrane potential (MMP), cellular respiration, and glycolysis in TNBC cell lines.
• Utilized human-induced pluripotent stem cell-derived cardiomyocytes as a non-cancerous mitochondrial-rich model.
• Employed two in vivo TNBC models to assess tumor growth, metastasis, and organ function.

Main Results:

• EP treatment reduced MMP and disrupted mitochondrial function specifically in TNBC cells, not in cardiomyocytes.
• In vivo studies showed EP significantly reduced tumor volume without adverse effects on liver function.
• EP treatment led to a significant decrease in lung and liver metastasis, as well as cancer stem cells.

Conclusions:

• Ergosterol peroxide selectively targets and disrupts mitochondrial function in TNBC cells.
• EP demonstrates significant anti-tumor and anti-metastatic effects in vivo.
• EP is a promising therapeutic agent for triple-negative breast cancer.