PTC596-Induced BMI-1 Inhibition Fights Neuroblastoma Multidrug Resistance by Inducing Ferroptosis
Abstract
:1. Introduction
2. Materials and Methods
2.1. Chemicals
2.2. Cell Cultures
2.3. Treatments
2.4. Cell Viability Assay (MTS)
2.5. Total Protein Extraction and Quantification
2.6. Western Blot Analysis
2.7. Clonogenic Assay
2.8. Cancer Stem Cell Formation Assessment
2.9. H2O2 Level Determination
2.10. HPLC Analysis of Intracellular GSH Levels
2.11. Lipid Peroxidation Assay
2.12. GPX4 Activity
2.13. Statistical Analysis
3. Results
3.1. HTLA-ER Developed a Multidrug-Resistant Phenotype
3.2. PTC596 Affects the Viability of Parental and HTLA-ER Cells and Reduces BMI-1 Expression Levels
3.3. PTC596 Does Not Alter the Expression of Apoptotic Proteins in Parental and HTLA-ER Cells
3.4. PRIMA-1MET and PTC596 Alone or in Combination Strongly Reduce the Clonogenic Potential of Parental and HTLA-ER Cells
3.5. PRIMA-1MET and PTC596, Alone or in Combination, Reduce the Expression of Crucial EMT-Promoting Proteins and Inhibit CSC Formation
3.6. PRIMA-1MET and PTC596, Alone or in Combination, Enhance H2O2 Production, Deplete Intracellular GSH, and Induce Lipid Peroxidation
3.7. PTC596 Exerts Its Cytotoxic Effect by Inducing Ferroptosis
4. Discussion
5. Conclusions
Author Contributions
Funding
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Drug | Dose Compared with That Clinically Used | HTLA-230 Cells’ IC50 | HTLA-ER Cells’ IC50 |
---|---|---|---|
Etoposide (μM) | 1.25 | 69.79 | 221.4 |
Doxorubicin (μM) | 0.05 | 3.21 | 8.88 |
Cyclophosphamide (mM) | 0.1 | 5.30 | 14.86 |
Cisplatin (μM) | 0.33 | 19.78 | 54.58 |
Carboplatin (μM) | 10 | 509.3 | 1345.02 |
Vincristine (nM) | 2.5 | 51.6 | 234.66 |
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Valenti, G.E.; Roveri, A.; Venerando, R.; Menichini, P.; Monti, P.; Tasso, B.; Traverso, N.; Domenicotti, C.; Marengo, B. PTC596-Induced BMI-1 Inhibition Fights Neuroblastoma Multidrug Resistance by Inducing Ferroptosis. Antioxidants 2024, 13, 3. https://doi.org/10.3390/antiox13010003
Valenti GE, Roveri A, Venerando R, Menichini P, Monti P, Tasso B, Traverso N, Domenicotti C, Marengo B. PTC596-Induced BMI-1 Inhibition Fights Neuroblastoma Multidrug Resistance by Inducing Ferroptosis. Antioxidants. 2024; 13(1):3. https://doi.org/10.3390/antiox13010003
Chicago/Turabian StyleValenti, Giulia Elda, Antonella Roveri, Rina Venerando, Paola Menichini, Paola Monti, Bruno Tasso, Nicola Traverso, Cinzia Domenicotti, and Barbara Marengo. 2024. "PTC596-Induced BMI-1 Inhibition Fights Neuroblastoma Multidrug Resistance by Inducing Ferroptosis" Antioxidants 13, no. 1: 3. https://doi.org/10.3390/antiox13010003
APA StyleValenti, G. E., Roveri, A., Venerando, R., Menichini, P., Monti, P., Tasso, B., Traverso, N., Domenicotti, C., & Marengo, B. (2024). PTC596-Induced BMI-1 Inhibition Fights Neuroblastoma Multidrug Resistance by Inducing Ferroptosis. Antioxidants, 13(1), 3. https://doi.org/10.3390/antiox13010003