The Effect of BCR-ABL Specific Tyrosine Kinase Inhibitors on the Thioredoxin System in Chronic Myeloid Leukemia
Abstract
:1. Introduction
2. Materials and Methods
2.1. Cell Lines and Reagents
2.2. Cell Viability Assay
2.3. Transient Transfections
2.4. MTT Cell Proliferation Assay
2.5. Caspase-3 Activity Assay
2.6. Thioredoxin Reductase Activity Assay
2.7. ROS Levels
2.8. Reverse Transcriptase Quantitative PCR (RT-qPCR)
2.9. Western Blotting
2.10. Bioinformatics
2.11. Statistical Analysis
3. Results
3.1. The TRX System Is Upregulated in Chronic Myeloid Leukemia
3.2. The Efficacy of TKIs on CML Cell Proliferation
3.3. TKIS Induce Apoptosis in CML Cells
3.4. TKIs Induce Increased ROS Levels in CML Cells
3.5. TKIs Decrease TRXR Activity
3.6. TKIs Decrease mRNA Levels of the TRX System Genes
3.7. TKIs Decrease Protein Levels of TRX1 and TRXR1
3.8. Specific Knockdown of BCR-ABL Results in Suppression of the TRX System
4. Discussion
Supplementary Materials
Author Contributions
Funding
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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K562 | KU812 | KCL22 | ||||
---|---|---|---|---|---|---|
24 h | 48 h | 24 h | 48 h | 24 h | 48 h | |
Imatinib | >2 µM | 0.3 µM | 0.4 µM | 0.3 µM | 0.5 µM | 0.3 µM |
Dasatinib | >50 nM | 7.5 nM | 1 nM | 1 nM | 17.5 nM | 7.5 nM |
Ponatinib | >200 nM | 30 nM | 7.5 nM | 5 nM | 30 nM | 20 nM |
GNF-5 | 5 µM | 1.5 µM | >5 µM | 1 µM | 0.8 µM | 0.5 µM |
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Clapper, E.; Di Trapani, G.; Tonissen, K.F. The Effect of BCR-ABL Specific Tyrosine Kinase Inhibitors on the Thioredoxin System in Chronic Myeloid Leukemia. Hemato 2021, 2, 237-254. https://doi.org/10.3390/hemato2020014
Clapper E, Di Trapani G, Tonissen KF. The Effect of BCR-ABL Specific Tyrosine Kinase Inhibitors on the Thioredoxin System in Chronic Myeloid Leukemia. Hemato. 2021; 2(2):237-254. https://doi.org/10.3390/hemato2020014
Chicago/Turabian StyleClapper, Erin, Giovanna Di Trapani, and Kathryn F. Tonissen. 2021. "The Effect of BCR-ABL Specific Tyrosine Kinase Inhibitors on the Thioredoxin System in Chronic Myeloid Leukemia" Hemato 2, no. 2: 237-254. https://doi.org/10.3390/hemato2020014
APA StyleClapper, E., Di Trapani, G., & Tonissen, K. F. (2021). The Effect of BCR-ABL Specific Tyrosine Kinase Inhibitors on the Thioredoxin System in Chronic Myeloid Leukemia. Hemato, 2(2), 237-254. https://doi.org/10.3390/hemato2020014