The Identification of New c-FLIP Inhibitors for Restoring Apoptosis in TRAIL-Resistant Cancer Cells
Abstract
:1. Introduction
2. Materials and Methods
2.1. Molecular Modeling
2.1.1. The Homology Modeling of DED2s
2.1.2. The Identification of the Binding Site
2.1.3. The Docking of Chemical Libraries
2.1.4. Consensus Scoring Function
2.1.5. Hit Selection
2.2. Cell Culture
2.3. Reagents and Antibodies
2.4. Flow Cytometry Analysis
2.5. Recombinant Protein Production and Purification
2.6. Pull-Down Binding Assay
2.7. DISC Immunoprecipitation
2.8. Western Blot Analysis
2.9. Statistical Analysis
3. Results
3.1. Potential c-FLIP Inhibitors Selected by In Silico Screening
3.2. The Newly Identified c-FLIP Inhibitors Prevent DED–FADD/DED2–c-FLIP Interactions
3.3. Newly Identified Molecules Inhibit c-FLIP Recruitment into the DISC by Preventing Its Interaction with the FADD
3.4. c-FLIP Inhibitors Rescue TRAIL-Mediated Apoptosis
3.5. A Combination Treatment of TRAIL with c-FLIP-Targeting Molecules Restores Caspases-Dependent Apoptosis
4. Discussion
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Yaacoub, K.; Pedeux, R.; Lafite, P.; Jarry, U.; Aci-Sèche, S.; Bonnet, P.; Daniellou, R.; Guillaudeux, T. The Identification of New c-FLIP Inhibitors for Restoring Apoptosis in TRAIL-Resistant Cancer Cells. Curr. Issues Mol. Biol. 2024, 46, 710-728. https://doi.org/10.3390/cimb46010046
Yaacoub K, Pedeux R, Lafite P, Jarry U, Aci-Sèche S, Bonnet P, Daniellou R, Guillaudeux T. The Identification of New c-FLIP Inhibitors for Restoring Apoptosis in TRAIL-Resistant Cancer Cells. Current Issues in Molecular Biology. 2024; 46(1):710-728. https://doi.org/10.3390/cimb46010046
Chicago/Turabian StyleYaacoub, Katherine, Rémy Pedeux, Pierre Lafite, Ulrich Jarry, Samia Aci-Sèche, Pascal Bonnet, Richard Daniellou, and Thierry Guillaudeux. 2024. "The Identification of New c-FLIP Inhibitors for Restoring Apoptosis in TRAIL-Resistant Cancer Cells" Current Issues in Molecular Biology 46, no. 1: 710-728. https://doi.org/10.3390/cimb46010046
APA StyleYaacoub, K., Pedeux, R., Lafite, P., Jarry, U., Aci-Sèche, S., Bonnet, P., Daniellou, R., & Guillaudeux, T. (2024). The Identification of New c-FLIP Inhibitors for Restoring Apoptosis in TRAIL-Resistant Cancer Cells. Current Issues in Molecular Biology, 46(1), 710-728. https://doi.org/10.3390/cimb46010046