Targeting Lipocalin-2 in Inflammatory Breast Cancer Cells with Small Interference RNA and Small Molecule Inhibitors
Abstract
:1. Introduction
2. Results
2.1. LCN2 Protein Levels Are Increased in Inflammatory Breast Cancer Cell (IBC) Lines
2.2. LCN2-siRNA-Based Silencing Reduces Cell Colony Formation, Cell Invasion and Migration in IBC Cells
2.3. LCN2 Silencing Induces Apoptosis and Cell Cycle Arrest
2.4. Identification of LCN2 Small Molecule Inhibitors by In-Silico Analysis
2.5. LCN2-Inhibitors Reduce Colony Formation and Cell Viability in SUM149 Cells
2.6. The LCN2 Inhibitors ZINC00784494 and ZINC00640089 Reduced the p-Akt Levels in SUM149 Cells
2.7. LCN2-Inhibitors ZINC00784494 and ZINC00640089 Showed Specificity toward LCN2
3. Discussion
4. Materials and Methods
4.1. Cell Culture
4.2. Western Blot Analysis
4.3. Transient and Stable Transfections
4.4. Colony Formation Assays
4.5. Cell Viability Assays
4.6. Invasion and Migration Assays
4.7. In Vitro Testing of Small Molecules Inhibitors
4.8. Akt/p-Akt Measurements
4.9. Caspase-3 Fluorometric Assay
4.10. Flow Cytometry Analysis
4.11. Molecular Docking
4.12. Physicochemical and Pharmacokinetic Properties
4.13. Statistical Analysis
5. Conclusions
6. Patents
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Santiago-Sánchez, G.S.; Noriega-Rivera, R.; Hernández-O’Farrill, E.; Valiyeva, F.; Quiñones-Diaz, B.; Villodre, E.S.; Debeb, B.G.; Rosado-Albacarys, A.; Vivas-Mejía, P.E. Targeting Lipocalin-2 in Inflammatory Breast Cancer Cells with Small Interference RNA and Small Molecule Inhibitors. Int. J. Mol. Sci. 2021, 22, 8581. https://doi.org/10.3390/ijms22168581
Santiago-Sánchez GS, Noriega-Rivera R, Hernández-O’Farrill E, Valiyeva F, Quiñones-Diaz B, Villodre ES, Debeb BG, Rosado-Albacarys A, Vivas-Mejía PE. Targeting Lipocalin-2 in Inflammatory Breast Cancer Cells with Small Interference RNA and Small Molecule Inhibitors. International Journal of Molecular Sciences. 2021; 22(16):8581. https://doi.org/10.3390/ijms22168581
Chicago/Turabian StyleSantiago-Sánchez, Ginette S., Ricardo Noriega-Rivera, Eliud Hernández-O’Farrill, Fatma Valiyeva, Blanca Quiñones-Diaz, Emilly S. Villodre, Bisrat G. Debeb, Andrea Rosado-Albacarys, and Pablo E. Vivas-Mejía. 2021. "Targeting Lipocalin-2 in Inflammatory Breast Cancer Cells with Small Interference RNA and Small Molecule Inhibitors" International Journal of Molecular Sciences 22, no. 16: 8581. https://doi.org/10.3390/ijms22168581