A Histone Deacetylase Inhibitor Manifests Synergistic Interaction with Artesunate by Suppressing DNA Repair Activity
Abstract
:1. Introduction
2. Materials and Methods
2.1. Chemicals and Reagents
2.2. Cell Culture and Drug Treatment
2.3. Assessment of Cell Viability
2.4. HDAC Inhibition Assay
2.5. Propidium Iodide (PI) Apoptosis Assay
2.6. Fluoremetric Analyses of Apoptotic Cells Using PE Annexin V and 7-AAD
2.7. Combination Index (CI) Curve and Isobologram Analyses
2.8. Intracellular ROS Measurement
2.9. Cell Cycle Analysis
2.10. Relative mRNA Expression Analysis
2.11. In Vivo Study
2.12. Dalton’s Ascites Lymphoma Development in Mice
2.13. In Vivo Experimental Design
2.14. Histopathological Analysis
2.15. Cell Viability Assay
2.16. Statistical Analysis
3. Results
3.1. 4-PB Cytotoxicity on MCF-7 and MDA-MB-231 Cells as a Consequence of HDAC Activity Inhibition
3.2. 4-PB Enhanced the Dose-Dependent Cytotoxicity of ART
3.3. Induction of Apoptosis by ART and/or 4-PB
3.4. Isobologram Depicted the Interaction of 4-PB with ART Is Synergistic
3.5. 4-PB and ART Increased Oxidative Stress in MCF7 Cells
3.6. Cell Cycle Perturbation after Treatment with ART and/or 4-PB
3.7. Mechanism Underlying 4-PB Mediated Enhanced ART DNA Damaging Effect
3.8. Therapeutic Effectivity of Combinated Drusg in a Murine Model
4. Discussion
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Ethics Approval
References
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S. No | Treatment | Viable Cell Count (105 Cells/mL) |
---|---|---|
1 | DLA + Saline | 418.4 ± 19.7 |
2 | DLA + 4-PB | 10.35 ± 1.5 * |
3 | DLA + Artesunate | 5.82 ± 1.4 * |
4 | DLA + 4-PB + Artesunate | 2.47 ± 0.8 * |
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Raza, A.; Kandimalla, R.; Kalita, S.; Ghosh, S.S. A Histone Deacetylase Inhibitor Manifests Synergistic Interaction with Artesunate by Suppressing DNA Repair Activity. Sci 2022, 4, 41. https://doi.org/10.3390/sci4040041
Raza A, Kandimalla R, Kalita S, Ghosh SS. A Histone Deacetylase Inhibitor Manifests Synergistic Interaction with Artesunate by Suppressing DNA Repair Activity. Sci. 2022; 4(4):41. https://doi.org/10.3390/sci4040041
Chicago/Turabian StyleRaza, Asif, Raghuram Kandimalla, Sanjeeb Kalita, and Siddhartha Sankar Ghosh. 2022. "A Histone Deacetylase Inhibitor Manifests Synergistic Interaction with Artesunate by Suppressing DNA Repair Activity" Sci 4, no. 4: 41. https://doi.org/10.3390/sci4040041