Use of Enzymatically Activated Carbon Monoxide Donors for Sensitizing Drug-Resistant Tumor Cells
Abstract
:1. Introduction
2. Results
2.1. Chemistry
2.2. Stability Studies
2.3. Biological Studies
2.3.1. CORM Is Effectively Taken Up by Drug-Resistant Cancer Cells Lines and Overcomes Resistance to Multiple Chemotherapeutic Drugs
2.3.2. CORM Alters Mitochondrial Energy Metabolism and Enhances Chemotherapy-Dependent Mitochondrial Apoptosis in Resistance Cells
2.3.3. CORM-Induced Chemosensitization Is Caused by Increased Oxidative Stress and CO Release
3. Discussion
4. Materials and Methods
4.1. Chemistry
4.1.1. Synthesis
4.1.2. Stability Assay
4.2. Biology
4.2.1. Cell Lines
4.2.2. CORM Intracellular Uptake and CO Release
4.2.3. Cell Viability
4.2.4. ABC Transporters Quantification and Activity
4.2.5. Mitochondrial Extraction, ETC and ATP Measurement
4.2.6. Mitochondrial Depolarization
4.2.7. ROS Measurement
4.2.8. Lipoperoxidation Assay
4.2.9. Caspase-9 and Caspase-3 Activation
4.2.10. Statistical Analysis
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Tumor Type | Cell Line | Drug Resistance to: | ABCB1 (% Positive Cells) | ABCC1 (% Positive Cells) | ABCC5 (% Positive Cells) |
---|---|---|---|---|---|
NSCLC | NCI-H2228 | Cisplatin [23] | 14.6 ± 1.5% | 76.6 ± 8.6% | 9.9 ± 0.7% |
NSCLC | A549 | Cisplatin [23] | 37.8 ± 2.3% | 89.6 ± 8.5% | 10.1 ± 1.2% |
TNBC | MDA-MB-231 | Doxorubicin, Docetaxel [24] | 55.9 ± 5.4% | 23.2 ± 3.7% | 34.8 ± 3.8% |
TNBC | MDA-MB-468 | Doxorubicin, Docetaxel [25] | 64.0 ± 5.0% | 14.9 ± 2.0% | 28.7 ± 2.3% |
PDAC | PANC-01 | Gemcitabine [26] | 10.7 ± 1.1% | 5.7 ± 2.0% | 71.3 ± 8.5% |
PDAC | Capan-1 | Gemcitabine [26] | 9.2 ± 1.0% | 4.6 ± 1.1% | 64.0 ± 4.2% |
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Sodano, F.; Rolando, B.; Lazzarato, L.; Costamagna, C.; Failla, M.; Riganti, C.; Chegaev, K. Use of Enzymatically Activated Carbon Monoxide Donors for Sensitizing Drug-Resistant Tumor Cells. Int. J. Mol. Sci. 2023, 24, 11258. https://doi.org/10.3390/ijms241411258
Sodano F, Rolando B, Lazzarato L, Costamagna C, Failla M, Riganti C, Chegaev K. Use of Enzymatically Activated Carbon Monoxide Donors for Sensitizing Drug-Resistant Tumor Cells. International Journal of Molecular Sciences. 2023; 24(14):11258. https://doi.org/10.3390/ijms241411258
Chicago/Turabian StyleSodano, Federica, Barbara Rolando, Loretta Lazzarato, Costanzo Costamagna, Mariacristina Failla, Chiara Riganti, and Konstantin Chegaev. 2023. "Use of Enzymatically Activated Carbon Monoxide Donors for Sensitizing Drug-Resistant Tumor Cells" International Journal of Molecular Sciences 24, no. 14: 11258. https://doi.org/10.3390/ijms241411258