Olaparib Synergizes the Anticancer Activity of Daunorubicin via Interaction with AKR1C3
Abstract
:Sample summary
Abstract
1. Introduction
2. Results
2.1. Screening for Interactions of Anthracycline Reductases with Olaparib
2.2. Olaparib Potently Inhibits Human Recombinant AKR1C3
2.3. Effect of Olaparib on AKR1C3-Mediated Daunorubicin Metabolism in HCT116 Cells
2.4. Olaparib Synergize with Daunorubicin due to Interaction with AKR1C3
2.5. Assessment of AKR1C3 Expression following Exposure to Olaparib
3. Discussion
4. Materials and Methods
4.1. Reagents and Chemicals
4.2. Cell Cultures
4.3. Cloning, Overexpression, and Purification of Recombinant CREs
4.4. Incubation Assay with Recombinant CREs
4.5. Docking Studies
4.6. Transient Transfection of HCT116 Cell Line
4.7. AKR1C3 Inhibitory Assay in HCT116 Cells
4.8. XTT Proliferation Assay
4.9. Drug Combination
4.10. Induction Studies
4.11. Ultra-High-Performance Liquid Chromatography (UHPLC)
4.12. Statistical Analysis
5. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
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Enzymes | Inhibition % Olaparib (10 µM) | Inhibition % Olaparib (50 µM) |
---|---|---|
AKR1C3 | 76.0 ± 0.32 | 91.4 ± 0.97 |
AKR1B10 | 0.0 | 7.7 ± 0.33 |
AKR1A1 | 1.8 ± 0.14 | 18.2 ± 0.39 |
AKR1B1 | 0.0 | 8.1 ± 0.83 |
CBR1 | 0.0 | 0.0 |
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Tavares, T.S.; Hofman, J.; Lekešová, A.; Želazková, J.; Wsól, V. Olaparib Synergizes the Anticancer Activity of Daunorubicin via Interaction with AKR1C3. Cancers 2020, 12, 3127. https://doi.org/10.3390/cancers12113127
Tavares TS, Hofman J, Lekešová A, Želazková J, Wsól V. Olaparib Synergizes the Anticancer Activity of Daunorubicin via Interaction with AKR1C3. Cancers. 2020; 12(11):3127. https://doi.org/10.3390/cancers12113127
Chicago/Turabian StyleTavares, Tássia S., Jakub Hofman, Alžběta Lekešová, Jana Želazková, and Vladimír Wsól. 2020. "Olaparib Synergizes the Anticancer Activity of Daunorubicin via Interaction with AKR1C3" Cancers 12, no. 11: 3127. https://doi.org/10.3390/cancers12113127