Senolytic Targeting of Bcl-2 Anti-Apoptotic Family Increases Cell Death in Irradiated Sarcoma Cells
Abstract
:Simple Summary
Abstract
1. Introduction
2. Results
2.1. RT Induces Proliferative Arrest in Sarcoma Cell Lines
2.2. Sarcoma Cell Lines Exhibit a Senescence Phenotype after Treatment
2.3. RT Modulates Bcl-2 Family of Anti-Apoptotic Proteins
2.4. Targeting Bcl-2 Family Proteins Specifically Eliminates Irradiated Sarcoma Cells
2.5. ABT-263 and ABT-199 Enhance Radiation Toxicity in a Three-Dimensional Model
3. Discussion
4. Materials and Methods
4.1. Cell Culture and Transduction
4.2. Irradiation and Senolytic Treatments
4.3. Clonogenic Assay
4.4. Cell Death and Cell Cycle Analysis by Flow Cytometry
4.5. Real-Time Imaging for Proliferation
4.6. Senescence-Associated β-Galactosidase Activity
4.7. EdU (5-Ethynyl-2′-Deoxyuridine) Detection
4.8. DNA-Damage Detection
4.9. Quantitative Real-Time PCR
4.10. List of Primers
4.11. Western Blot Analysis
4.12. Cytokine Secretion Measurement
4.13. Real-Time Imaging for Cell Death and Apoptosis
4.14. Drug Combination Analysis
4.15. 3D Cell Culture
4.16. Statistical Analysis
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
53BP1 | Tumor suppressor p53-binding protein 1 |
Bcl-2 | B-cell lymphoma 2 |
Bcl-xL | B-cell lymphoma-extra large |
BH3 | Bcl-2 homology domain 3 |
BSA | Bovine serum albumin |
DAPI | 4′,6-diamidino-2-phenylindole fluorescent stain |
DMEM | Dulbecco’s modified eagle medium |
DMSO | Dimethyl sulfoxide |
EdU | 5-Ethynyl-2’-deoxyuridine |
FACS | Fluorescent activated cell sorting |
FBS | Fetal bovine serum |
FDA | Food and drug administration |
GFP | Green fluorescent protein |
H2B | Histone H2B |
HRPT | Hypoxanthine Phosphoribosyltransferase 1 |
HRP | Horseradish peroxidase |
IL-6 | Interleukin 6 |
IL-8 | Interleukin 8 |
IMRT | Intensity-modulated radiation therapy |
LR | Local recurrence |
MCL-1 | Induced myeloid leukemia cell differentiation protein |
PARP | Poly (ADP-ribose) polymerase |
PBS | Phosphate-buffered saline |
PI | Propidium iodide |
PVDF | Polyvinylidene fluoride |
RT | Radiation therapy |
SASP | Senescence associated secretory phenotype |
SA-β-gal | Senescence associated beta-galactosidase |
SBRT | Stereotactic body radiation therapy |
STS | Soft-tissue sarcoma |
TBP | TATA-binding protein gene expression |
TIS | Therapy-induced senescence |
UPS | Undifferentiated pleomorphic sarcoma |
γH2AX | Phosphorylated H2AX (Ser139) |
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Lafontaine, J.; Cardin, G.B.; Malaquin, N.; Boisvert, J.-S.; Rodier, F.; Wong, P. Senolytic Targeting of Bcl-2 Anti-Apoptotic Family Increases Cell Death in Irradiated Sarcoma Cells. Cancers 2021, 13, 386. https://doi.org/10.3390/cancers13030386
Lafontaine J, Cardin GB, Malaquin N, Boisvert J-S, Rodier F, Wong P. Senolytic Targeting of Bcl-2 Anti-Apoptotic Family Increases Cell Death in Irradiated Sarcoma Cells. Cancers. 2021; 13(3):386. https://doi.org/10.3390/cancers13030386
Chicago/Turabian StyleLafontaine, Julie, Guillaume B. Cardin, Nicolas Malaquin, Jean-Sébastien Boisvert, Francis Rodier, and Philip Wong. 2021. "Senolytic Targeting of Bcl-2 Anti-Apoptotic Family Increases Cell Death in Irradiated Sarcoma Cells" Cancers 13, no. 3: 386. https://doi.org/10.3390/cancers13030386