Coupling Kinesin Spindle Protein and Aurora B Inhibition with Apoptosis Induction Enhances Oral Cancer Cell Killing
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Small Molecule Inhibitors
2.2. Cell Culture
2.3. RNA Extraction, cDNA Synthesis, and Real-Time PCR
2.4. Protein Extraction and Western Blotting
2.5. Indirect Immunofluorescence
2.6. MTT Assay
2.7. Apoptosis Detection Using Annexin V/PI Staining
2.8. Mitotic Index Determination
2.9. Time-Lapse Microscopy
2.10. Phase-Contrast and Fluorescence Microscopy Images
2.11. Colony Formation Assay
2.12. Statistical Analysis
3. Results
3.1. KSP and Aurora B Proteins Are Overexpressed in Oral Squamous Carcinoma Cells
3.2. The Combinatorial Approaches with Ispinesib and Navitoclax and Barasertib with Navitoclax Show Synergistic Effects in Oral Cancer Cells
3.3. The Combined Treatment with Ispinesib and Navitoclax Enhances Death in Mitosis in Oral Cancer Cells
3.4. Combining Barasertib-Mediated Aurora B Inhibition with Navitoclax Shifts the Cancer Cell Fate from Post-Slippage Cell Survival to Post-Slippage Cell Death
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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IC50 (nM) | ||
---|---|---|
Drugs|Cell Line | SCC25 | SCC09 |
Navitoclax | 5197.0 ± 364.0 | 3754.0 ± 237.0 |
Ispinesib | 3.4 ± 0.5 | 58.9 ± 3.2 |
Barasertib | 5580.0 ± 664.0 | >64,000.0 |
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Silva, J.P.N.; Pinto, B.; Monteiro, L.; Silva, P.M.A.; Bousbaa, H. Coupling Kinesin Spindle Protein and Aurora B Inhibition with Apoptosis Induction Enhances Oral Cancer Cell Killing. Cancers 2024, 16, 2014. https://doi.org/10.3390/cancers16112014
Silva JPN, Pinto B, Monteiro L, Silva PMA, Bousbaa H. Coupling Kinesin Spindle Protein and Aurora B Inhibition with Apoptosis Induction Enhances Oral Cancer Cell Killing. Cancers. 2024; 16(11):2014. https://doi.org/10.3390/cancers16112014
Chicago/Turabian StyleSilva, João P. N., Bárbara Pinto, Luís Monteiro, Patrícia M. A. Silva, and Hassan Bousbaa. 2024. "Coupling Kinesin Spindle Protein and Aurora B Inhibition with Apoptosis Induction Enhances Oral Cancer Cell Killing" Cancers 16, no. 11: 2014. https://doi.org/10.3390/cancers16112014