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

Ergosterol peroxide (EP) triggers apoptosis pathways by inducing reactive oxygen species (ROS) in TNBC cell lines. Excess ROS production is associated with major damage to mitochondria. We hypothesized that EP may act through ROS-induced mitochondrial dysfunction. Therefore, we performed a series of assays that assessed mitochondrial membrane potential (MMP), cellular respiration, and glycolysis in TNBC models. Cardiomyocytes derived from human-induced pluripotent stem cells were chosen as a non-cancerous model because of their high mitochondrial content. Two in vivo TNBC models were used to quantify the effect of EP on tumor volume and metastases. EP reduced MMP and disrupted mitochondrial functions exclusively in TNBC cells. In vivo EP was effective in reducing tumor volume without affecting liver function. There was also a significant decrease in metastasis to the lung, liver, and cancer stem cells following treatment. These results suggest EP is a promising therapy for TNBC.