Impairment of Hypoxia-Induced CA IX by Beta-Blocker Propranolol—Impact on Progression and Metastatic Potential of Colorectal Cancer Cells
Abstract
:1. Introduction
2. Results
2.1. Expression of Beta Adrenoreceptors in Colorectal Carcinomas-In Silico Analysis
2.2. Expression of β-AR in Colorectal Carcinoma Tissues
2.3. Beta-Blockade by Propranolol Influences Extracellular pH of Colorectal Cancer Cells in Hypoxia
2.4. Beta-Blockade by Propranolol Decreases Level of Phosphorylated form of Catalytic Subunit of PKA under Hypoxic Conditions
2.5. Propranolol Decreases Expression of CA IX in Hypoxic Colorectal Cancer Cells Cultivated in Monolayer
2.6. Propranolol Influences Adaptation to Hypoxic Microenvironment by Decreased Levels of HIF1α and CA IX in 3D Spheroids
2.7. Propranolol Decreases Migration Properties of Colorectal Cancer Cells
2.8. Distribution of CA IX in 3D Spheroids Is Polarized
2.9. Propranolol Affects Cell Stress Proteome in Spheroids
2.10. Propranolol Reduces Number of Mitochondria and Mitochondrial ox-phos Enzymes
3. Discussion
4. Materials and Methods
4.1. Cell Culture and Growth Conditions
4.2. Western Blotting
4.3. Proteome Profiler Array
4.4. Flow Cytometry Analysis of Cell Viability
4.5. Quantitative Real-Time PCR
4.6. Formation of Spheroids in Hanging Drops
4.7. Clonogenic Assay
4.8. Immunofluorescence of Spheroids
4.9. Immunohistochemistry
4.10. In Silico Analysis
4.11. Time-Lapse Microscopy
4.12. Fluorescent Labelling and Analysis of Mitochondrial Network
4.13. Ethic Approval and Patients Tissue Samples
4.14. Statistical Analysis
5. Conclusions
Author Contributions
Funding
Conflicts of Interest
Abbreviations
CA IX | Carbonic anhydrase IX |
β-AR | Beta adrenergic receptor |
HIF1 | Hypoxia inducible factor 1 |
PKA | Protein kinase A |
References
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Barathova, M.; Grossmannova, K.; Belvoncikova, P.; Kubasova, V.; Simko, V.; Skubla, R.; Csaderova, L.; Pastorek, J. Impairment of Hypoxia-Induced CA IX by Beta-Blocker Propranolol—Impact on Progression and Metastatic Potential of Colorectal Cancer Cells. Int. J. Mol. Sci. 2020, 21, 8760. https://doi.org/10.3390/ijms21228760
Barathova M, Grossmannova K, Belvoncikova P, Kubasova V, Simko V, Skubla R, Csaderova L, Pastorek J. Impairment of Hypoxia-Induced CA IX by Beta-Blocker Propranolol—Impact on Progression and Metastatic Potential of Colorectal Cancer Cells. International Journal of Molecular Sciences. 2020; 21(22):8760. https://doi.org/10.3390/ijms21228760
Chicago/Turabian StyleBarathova, Monika, Katarina Grossmannova, Petra Belvoncikova, Veronika Kubasova, Veronika Simko, Rudolf Skubla, Lucia Csaderova, and Jaromir Pastorek. 2020. "Impairment of Hypoxia-Induced CA IX by Beta-Blocker Propranolol—Impact on Progression and Metastatic Potential of Colorectal Cancer Cells" International Journal of Molecular Sciences 21, no. 22: 8760. https://doi.org/10.3390/ijms21228760