Chloroquine-Induced DNA Damage Synergizes with Nonhomologous End Joining Inhibition to Cause Ovarian Cancer Cell Cytotoxicity
Abstract
:1. Introduction
2. Results
2.1. Panobinostat Does Not Affect NHEJ Efficiency in OCCLs
2.2. Chloroquine Induces DSBs, Which Are Repaired by NHEJ
2.3. NHEJ Inhibitors Decrease Proliferation Rates and Induce Apoptosis in OCCLs
2.4. Combination of Chloroquine and NHEJ Inhibitors Synergistically Induces Cell Death in OCCLs
2.5. Cell Death Induced by the Combination of CQ and NHEJ Inhibitors Depends on ROS Production
2.6. The Triple Combination CQ-NHEJi-LBH Exerts a Strong Synergy and Higher Efficacy Compared with Double Combinations
3. Discussion
4. Materials and Methods
4.1. Cell Lines and Culture Conditions
4.2. Reagents
4.3. Western Blot
4.4. NHEJ Assays
4.5. Construction of Cell Lines for Detecting NHEJ Efficiency
4.6. Cell Proliferation Assay
4.7. Cell Cycle Analysis
4.8. Apoptosis Assay
4.9. Immunofluorescence
4.10. Statistical Analysis
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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Cell Line | A2780 | IGROV-1 | OVCAR-8 | SK-OV-3 |
---|---|---|---|---|
Inhibitors | IC50 (95% CI) | IC50 (95% CI) | IC50 (95% CI) | IC50 (95% CI) |
KU-57788 | 2.56 µM (2.25–2.89 µM) | 1.86 µM (1.62–2.12 µM) | 3.42 µM (2.81–4.14 µM) | 11.07 µM (9.07–13.51 µM) |
NU-7026 | 2.51 µM (2.10–2.97 µM) | 0.96 µM (0.81–1.12 µM) | 4.27 µM (3.45–5.26 µM) | 7.30 µM (6.38–8.36 µM) |
SCR7 | 204.5 µM (129.7–348.8 µM) | 329.8 µM (253.1–446.9 µM) | 305.4 µM (223.2–439.4 µM) | 269.5 µM (202.3–373.1 µM) |
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Ovejero-Sánchez, M.; Rubio-Heras, J.; Vicente de la Peña, M.d.C.; San-Segundo, L.; Pérez-Losada, J.; González-Sarmiento, R.; Herrero, A.B. Chloroquine-Induced DNA Damage Synergizes with Nonhomologous End Joining Inhibition to Cause Ovarian Cancer Cell Cytotoxicity. Int. J. Mol. Sci. 2022, 23, 7518. https://doi.org/10.3390/ijms23147518
Ovejero-Sánchez M, Rubio-Heras J, Vicente de la Peña MdC, San-Segundo L, Pérez-Losada J, González-Sarmiento R, Herrero AB. Chloroquine-Induced DNA Damage Synergizes with Nonhomologous End Joining Inhibition to Cause Ovarian Cancer Cell Cytotoxicity. International Journal of Molecular Sciences. 2022; 23(14):7518. https://doi.org/10.3390/ijms23147518
Chicago/Turabian StyleOvejero-Sánchez, María, Jorge Rubio-Heras, María del Carmen Vicente de la Peña, Laura San-Segundo, Jesús Pérez-Losada, Rogelio González-Sarmiento, and Ana Belén Herrero. 2022. "Chloroquine-Induced DNA Damage Synergizes with Nonhomologous End Joining Inhibition to Cause Ovarian Cancer Cell Cytotoxicity" International Journal of Molecular Sciences 23, no. 14: 7518. https://doi.org/10.3390/ijms23147518