The New Microtubule-Targeting Agent SIX2G Induces Immunogenic Cell Death in Multiple Myeloma
Abstract
:1. Introduction
2. Results
2.1. SIX2G Could Sterically Prevent PP1/GADD34 Association by Inducing Immunogenic Cell Death
2.2. SIX2G Inhibits Cell Viability and Induces Apoptosis of Multiple Myeloma Cells
2.3. SIX2G Induces Alteration in Mitotic-Spindle and Apical Junction Pathways and Triggers Cell Cycle Arrest in G2/M Phases
2.4. SIX2G Induces Calreticulin Exposure and ATP Release by Activating an Immunogenic Cascade
2.5. SIX2G Treatment on Tumor Cells Promotes DC Maturation, Activation and Cross-Priming
3. Discussion
4. Materials and Methods
4.1. Chemical Synthesis of SIX2G
4.2. Docking Simulations
4.3. Cell Cultures
4.4. Dentric Cells Generation
4.5. Cell Viability, Apoptosis and Cell Cycle Analysis
4.6. Gene Expression Profiling
4.7. Western Blot Analysis
4.8. Calreticulin Exposure and ATP Release Analyses
4.9. DC Maturation and Phagocytosis Assay
4.10. DC Cross-Priming
4.11. Statistical Analysis
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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PDB Model | ΔGbind | ΔGCoul | ΔGLipo | ΔGSolv | ΔGvdW |
---|---|---|---|---|---|
3E7A chain A | −51.72 | −17.78 | −29.04 | 27.20 | −29.61 |
3E7A chain B | −46.90 | −13.12 | −25.99 | 23.24 | −30.87 |
3E7B chain A | −42.50 | −7.76 | −28.00 | 22.98 | −30.99 |
3E7B chain B | −39.70 | −1.79 | −28.62 | 18.86 | −31.61 |
4XPN chain A | −41.56 | −6.96 | −22.45 | 14.25 | −22.46 |
4XPN chain B | −53.17 | −13.14 | −31.37 | 23.57 | −30.97 |
3EGG chain A | −57.66 | −11.89 | −34.15 | 20.25 | −32.64 |
3EGG chain B | −57.33 | −12.70 | −33.59 | 21.36 | −30.69 |
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Grillone, K.; Riillo, C.; Rocca, R.; Ascrizzi, S.; Spanò, V.; Scionti, F.; Polerà, N.; Maruca, A.; Barreca, M.; Juli, G.; et al. The New Microtubule-Targeting Agent SIX2G Induces Immunogenic Cell Death in Multiple Myeloma. Int. J. Mol. Sci. 2022, 23, 10222. https://doi.org/10.3390/ijms231810222
Grillone K, Riillo C, Rocca R, Ascrizzi S, Spanò V, Scionti F, Polerà N, Maruca A, Barreca M, Juli G, et al. The New Microtubule-Targeting Agent SIX2G Induces Immunogenic Cell Death in Multiple Myeloma. International Journal of Molecular Sciences. 2022; 23(18):10222. https://doi.org/10.3390/ijms231810222
Chicago/Turabian StyleGrillone, Katia, Caterina Riillo, Roberta Rocca, Serena Ascrizzi, Virginia Spanò, Francesca Scionti, Nicoletta Polerà, Annalisa Maruca, Marilia Barreca, Giada Juli, and et al. 2022. "The New Microtubule-Targeting Agent SIX2G Induces Immunogenic Cell Death in Multiple Myeloma" International Journal of Molecular Sciences 23, no. 18: 10222. https://doi.org/10.3390/ijms231810222