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

Sep 23, 2026

Ergosterol peroxide (EP) activates apoptosis pathways in triple-negative breast cancer (TNBC) cell lines by inducing reactive oxygen species (ROS), where excessive ROS damages mitochondria. The study tests the hypothesis that EP acts via ROS-driven mitochondrial dysfunction. A set of assays evaluates mitochondrial membrane potential, cellular respiration, and glycolysis across TNBC models, using cardiomyocytes from human-induced pluripotent stem cells as a non-cancer control. Two in vivo TNBC models measure tumor volume and metastasis after EP treatment. EP lowers mitochondrial membrane potential and disrupts mitochondrial functions specifically in TNBC cells, reducing tumor volume without affecting liver function and decreasing lung, liver, and cancer stem cell metastasis. The results support EP as a promising TNBC therapy.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages16

Reading Time40 min

AccessFree to download

Abstract

Keywords

Introduction

Breast cancer burden and TNBC features

Limitations of systemic chemotherapy

Natural product lead compounds and prior work

Article Ergosterol Peroxide Disrupts Triple-Negative Breast Cancer Mitochondrial Function and Inhibits Tumor Growth and Metastasis Aliyah L. Bocachica-Adorno 1, Adriana Y. Aponte-Ramos 2, Paola S. Rivera-Fuentes 3, Natalia P. Espinosa-Ponce 1, Luz V. Arroyo-Cruz 4, Taotao Ling 5, Naydi Pérez-Ríos 6, Sona Rivas-Tumanyan 6,7, Israel A. Almodóvar-Rivera 8, Carlos Barreto-Gamarra 9, Maribella Domenech-García 9, Fatima Rivas 5 and Michelle M. Martínez-Montemayor 4, * Academic Editor: Jennifer Sims-Mourtada Received: 7 April 2025 Revised: 5 May 2025 Accepted: 8 May 2025 Published: 10 May 2025 Citation: Bocachica-Adorno, A.L.; Aponte-Ramos, A.Y.; Rivera-Fuentes, P.S.; Espinosa-Ponce, N.P.; Arroyo-Cruz, L.V.; Ling, T.; Pérez-Ríos, N.; Rivas-Tumanyan, S.; Almodóvar-Rivera, I.A.; BarretoGamarra, C.; et al. Ergosterol Peroxide Disrupts Triple-Negative Breast Cancer Mitochondrial Function and Inhibits Tumor Growth and Metastasis. Int. J. Mol. Sci. 2025, 26, 4588. [https://](https://)[ ](https://)[doi.org/10.3390/ijms26104588](doi.org/10.3390/ijms26104588) [Copyright:](Copyright:) © 2025 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ([https://creativecommons.org/](https://creativecommons.org/)[ ](https://creativecommons.org/)[licenses/by/4.0/](licenses/by/4.0/)) . 1 Department of Biology, University of Puerto Rico at Bayamón, Bayamón, PR 00959, USA; [aliyah.bocachica@upr.edu](aliyah.bocachica@upr.edu) (A.L.B.-A.); [natalia.espinosa@upr.edu](natalia.espinosa@upr.edu) (N.P.E.-P.) 2 Department of Biology, Inter American University of Puerto Rico at Bayamón, Bayamón, PR 00957, USA; [yanellyaponte6@gmail.com](yanellyaponte6@gmail.com) 3 Department of Biology, University of Puerto Rico at Río Piedras, San Juan, PR 00935, USA; [paola.rivera115@upr.edu](paola.rivera115@upr.edu) 4 Department of Biochemistry, Universidad Central del Caribe-School of Medicine, Bayamón, PR 00960, USA; [luz.arroyo@uccaribe.edu](luz.arroyo@uccaribe.edu) 5 Department of Chemistry, Louisiana State University, Baton Rouge, LA 70803, USA; [tling@lsu.edu](tling@lsu.edu) (T.L.); [frivas@lsu.edu](frivas@lsu.edu) (F.R.) 6 Hispanic Alliance for Clinical and Translational Research, University of Puerto Rico-Medical Sciences Campus, San Juan, PR 00936, USA; [naydi.perez@upr.edu](naydi.perez@upr.edu) (N.P.-R.); [sona.tumanyan@upr.edu](sona.tumanyan@upr.edu) (S.R.-T.) 7 Department of Surgical Sciences and the Office of the Assistant Dean for Research, School of Dental Medicine, University of Puerto Rico, San Juan, PR 00936, USA 8 Department of Mathematical Sciences, University of Puerto Rico at Mayagüez, Mayagüez, PR 00689, USA; [israel.almodovar@upr.edu](israel.almodovar@upr.edu) 9 Department of Chemical Engineering, University of Puerto Rico at Mayagüez, Mayagüez, PR 00689, USA; [carlos.barreto7@upr.edu](carlos.barreto7@upr.edu) (C.B.-G.); [maribella.domenech@upr.edu](maribella.domenech@upr.edu) (M.D.-G.) * [Correspondence: michelle.martinez@uccaribe.edu or mmmtz92@gmail.com](Correspondence: michelle.martinez@uccaribe.edu or mmmtz92@gmail.com); Tel.: +1-787-798-3001 (ext. 2152) Abstract: 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 TN

FAQs

How does ergosterol peroxide affect TNBC cells in vitro?

Ergosterol peroxide induces reactive oxygen species, which triggers apoptosis pathways. It reduces mitochondrial membrane potential and disrupts mitochondrial function specifically in TNBC cells.

What mitochondrial and metabolic assays were used to test the mechanism?

The study measured mitochondrial membrane potential, cellular respiration, and glycolysis in TNBC models to assess mitochondrial dysfunction linked to ROS.

What were the in vivo effects of ergosterol peroxide on tumors and metastasis?

In two TNBC models, ergosterol peroxide reduced tumor volume without affecting liver function. It also significantly decreased metastasis to the lung and liver and reduced cancer stem cell-associated metastasis after treatment.

Sep 23, 2026

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