Small Extracellular Vesicles from Breast Cancer Cells Induce Cardiotoxicity
Abstract
1. Introduction
2. Results
2.1. Optimal Doxorubicin Concentration for sEVs Isolation from MCF-7 Cancer Cells
2.2. Isolation and Characterization of sEVs from Conditioned Media of Doxo-Treated MCF-7 Cells
2.3. Differential Cytokine Profile in Doxorubicin-Exposed MCF-7 sEVs
2.4. Effect of MCF-7-Derived sEVs on Cardiomyocyte Viability, Cellular Morphology, Oxidative Stress, Intracellular Calcium Levels, and Mitochondrial Membrane Potential in Isolated Guinea Pig Cardiomyocytes
3. Discussion
3.1. Optimizing Doxorubicin Concentration to Induce Cytotoxic Stress in MCF-7 Cells for sEV Isolation and Functional Analysis
3.2. Effective sEVs Isolation and Characterization from MCF-7 Cells
3.3. Cytokine Profile of sEVs from Doxorubicin-Treated MCF-7 Cells
3.4. Cardiotoxic Effects of sEVs from MCF-7 Cells on Isolated Cardiomyocytes
- Study limitations, challenges/future focus
- Clinical perspectives
4. Materials and Methods
4.1. Cell Culture and Doxorubicin Treatment
4.2. Isolation of Extracellular Vesicles and Characterization Using Nanoparticle Tracking Analysis (NTA) and Western Blot
4.3. Scanning Transmission Electron Microscopy (STEM)
4.4. sEVs Lysis and Cytokine Profiling
4.5. Cardiomyocyte Isolation, Vesicle Treatment, and Imaging Analysis
4.6. ROS Levels Assessment in Cardiomyocytes with DHE Dye
4.7. Mitochondrial Membrane Potential Assessment in Cardiomyocytes with JC-1 Dye
4.8. Evaluation of Intracellular Calcium Levels by Fluo-4 AM Reagent
4.9. Statistical Analysis
- Interpretation of Cohen’s d:
- Small effect: 0.2 ≤ d < 0.5;
- Medium effect: 0.5 ≤ d < 0.8;
- Large effect: d ≥ 0.8.
- Interpretation of η2:
- Small effect: 0.01 ≤ η2 < 0.060;
- Medium effect: 0.06 ≤ η2 < 0.140;
- Large effect: η2 ≥ 0.14.
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Osorio-Méndez, J.J.; Gómez-Grosso, L.A.; Montoya-Ortiz, G.; Novoa-Herrán, S.; Domínguez-Romero, Y. Small Extracellular Vesicles from Breast Cancer Cells Induce Cardiotoxicity. Int. J. Mol. Sci. 2025, 26, 945. https://doi.org/10.3390/ijms26030945
Osorio-Méndez JJ, Gómez-Grosso LA, Montoya-Ortiz G, Novoa-Herrán S, Domínguez-Romero Y. Small Extracellular Vesicles from Breast Cancer Cells Induce Cardiotoxicity. International Journal of Molecular Sciences. 2025; 26(3):945. https://doi.org/10.3390/ijms26030945
Chicago/Turabian StyleOsorio-Méndez, Jhon Jairo, Luis Alberto Gómez-Grosso, Gladis Montoya-Ortiz, Susana Novoa-Herrán, and Yohana Domínguez-Romero. 2025. "Small Extracellular Vesicles from Breast Cancer Cells Induce Cardiotoxicity" International Journal of Molecular Sciences 26, no. 3: 945. https://doi.org/10.3390/ijms26030945
APA StyleOsorio-Méndez, J. J., Gómez-Grosso, L. A., Montoya-Ortiz, G., Novoa-Herrán, S., & Domínguez-Romero, Y. (2025). Small Extracellular Vesicles from Breast Cancer Cells Induce Cardiotoxicity. International Journal of Molecular Sciences, 26(3), 945. https://doi.org/10.3390/ijms26030945