Antioxidant Defenses Confer Resistance to High Dose Melphalan in Multiple Myeloma Cells
Abstract
:1. Introduction
2. Results
2.1. Antioxidants Protect Cells from Melphalan-Induced Toxicity
2.2. Addition of GSH Prevents Cell Cycle Arrest after Treatment with Melphalan and Increases Resistance to High Dose Melphalan
2.3. GSH Efficiently Blocks Melphalan Induced Cell Death in Primary Myeloma Cells of Patients
2.4. Glutathione Did Not Affect the Ability of Melphalan to Induce DNA Lesions in MM Cells
2.5. Melphalan Treatment Induces ROS Production, which are Involved in Melphalan-Induced Cytotoxicity and Prevented by Addition of GSH
2.6. Melphalan Induces GSH Depletion Together with Protein and Lipid Oxidation
2.7. Oxidative Stress Response Score is Associated with a Poor Outcome in MM Patients
3. Discussion
4. Materials and Methods
4.1. Drugs and Reagents
4.2. Human Myeloma Cell Lines Culture (HMCLs)
4.3. Primary Plasma Cells Culture
4.4. Cell Growth Assay
4.5. Cell Cycle Analysis
4.6. Caspase 3/7 and 9 Activity
4.7. Gene Expression Profiling and Statistical Analyses
4.8. DNA Repair Foci Quantification
4.9. Detection of Intracellular Reactive Oxygen Species (ROS)
4.10. Reduced Glutathione Quantification
4.11. Protein Carbonyl Oxidation Assay
4.12. Malondialdehyde (MDA) Quantification Assay
4.13. Study of Apoptosis
4.14. Statistical Analysis
4.15. Western Blot Analysis
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Conflicts of Interest
References
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Gourzones, C.; Bellanger, C.; Lamure, S.; Gadacha, O.K.; De Paco, E.G.; Vincent, L.; Cartron, G.; Klein, B.; Moreaux, J. Antioxidant Defenses Confer Resistance to High Dose Melphalan in Multiple Myeloma Cells. Cancers 2019, 11, 439. https://doi.org/10.3390/cancers11040439
Gourzones C, Bellanger C, Lamure S, Gadacha OK, De Paco EG, Vincent L, Cartron G, Klein B, Moreaux J. Antioxidant Defenses Confer Resistance to High Dose Melphalan in Multiple Myeloma Cells. Cancers. 2019; 11(4):439. https://doi.org/10.3390/cancers11040439
Chicago/Turabian StyleGourzones, Claire, Céline Bellanger, Sylvain Lamure, Ouissem Karmous Gadacha, Elvira Garcia De Paco, Laure Vincent, Guillaume Cartron, Bernard Klein, and Jérôme Moreaux. 2019. "Antioxidant Defenses Confer Resistance to High Dose Melphalan in Multiple Myeloma Cells" Cancers 11, no. 4: 439. https://doi.org/10.3390/cancers11040439
APA StyleGourzones, C., Bellanger, C., Lamure, S., Gadacha, O. K., De Paco, E. G., Vincent, L., Cartron, G., Klein, B., & Moreaux, J. (2019). Antioxidant Defenses Confer Resistance to High Dose Melphalan in Multiple Myeloma Cells. Cancers, 11(4), 439. https://doi.org/10.3390/cancers11040439