NLRP3 as Putative Marker of Ipilimumab-Induced Cardiotoxicity in the Presence of Hyperglycemia in Estrogen-Responsive and Triple-Negative Breast Cancer Cells
Abstract
:1. Introduction
2. Results
2.1. CTLA-4 Expression in Human Breast Cancer Cells
2.2. Glucose Reduces Ipilimumab-Related Anticancer Activities and Increases its Cardiotoxicity
2.3. Glucose Increases Leukotriene-Mediated Cardiotoxicity of Ipilimumab
2.4. Hyperglycemia Have Pro-Oxidative Effects during Treatment with Ipilimumab
2.5. p65-NF-κB is Overexpressed under Hyperglicemic Condition
2.6. NLRP3 and MYD88 Expression Are Key Mediators of Hyperglicemia-Mediated Effects in Human Breast Cancer Cells and Cardiomyocytes
2.7. NLRP3 Staining in Breast Cancer Cells and Cardiomyocytes
2.8. Pro-Inflamamtory Cytokines and Growth Factors Are Overexpressed during Hyperglycemia
3. Discussion
4. Materials and Methods
4.1. Cell Culture
4.2. Co-Cultures
4.3. CTLA-4 Expression in Breast Cancer Cells through Flow Cytometry
4.4. Cell Viability
4.5. Expression of Leukotriene B4 (LTB4)
4.6. Reactive Oxygen Species and Lipid Peroxidation
4.7. p65-NF-κB Expression
4.8. NLRP3 and MyD88: Key Mediators of Hyperglycemia-Induced Cardiotoxicity
4.9. Confocal Laser Scanning Microscope
4.9.1. Cytokines and Growth Factors Assay
4.9.2. Statistical Analysis
5. Conclusions
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
Abbreviations
ICIs | Immune checkpoint inhibitors |
SGLT-2 | Sodium-glucose cotransporter type-2 |
NLRP3 | NOD-like receptor family pyrin domain, containing 3 |
MyD88 | Myddosome type 88 |
PD1 | Programmed cell death protein 1 |
PDL1 | Programmed Death-Ligand 1 |
CTLA4 | Cytotoxic T-Lymphocyte Antigen 4 |
AMPK | 5’ AMP-activated protein kinase |
hs-CRP | High sensitivity C-reactive protein |
ROS | Reactive oxygen species |
MDA | Malondialdeyde |
p65-NF-κB | Nuclear factor kappa-light-chain-enhancer of activated B cells |
ILs | Interleukins |
PDGF | Platelet-Derived Growth Factor |
VEGF | Vascular endothelia growth factor |
TGF-β | Transforming growth factor beta |
AGEs | Advanced glycation end products |
CVOTs | Cardiovascular outcome trials |
VEGF | Vascular endothelia growth factor |
TGF-β | Transforming growth factor beta |
AGEs | Advanced glycation end products |
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Quagliariello, V.; De Laurentiis, M.; Cocco, S.; Rea, G.; Bonelli, A.; Caronna, A.; Lombari, M.C.; Conforti, G.; Berretta, M.; Botti, G.; et al. NLRP3 as Putative Marker of Ipilimumab-Induced Cardiotoxicity in the Presence of Hyperglycemia in Estrogen-Responsive and Triple-Negative Breast Cancer Cells. Int. J. Mol. Sci. 2020, 21, 7802. https://doi.org/10.3390/ijms21207802
Quagliariello V, De Laurentiis M, Cocco S, Rea G, Bonelli A, Caronna A, Lombari MC, Conforti G, Berretta M, Botti G, et al. NLRP3 as Putative Marker of Ipilimumab-Induced Cardiotoxicity in the Presence of Hyperglycemia in Estrogen-Responsive and Triple-Negative Breast Cancer Cells. International Journal of Molecular Sciences. 2020; 21(20):7802. https://doi.org/10.3390/ijms21207802
Chicago/Turabian StyleQuagliariello, Vincenzo, Michelino De Laurentiis, Stefania Cocco, Giuseppina Rea, Annamaria Bonelli, Antonietta Caronna, Maria Cristina Lombari, Gabriele Conforti, Massimiliano Berretta, Gerardo Botti, and et al. 2020. "NLRP3 as Putative Marker of Ipilimumab-Induced Cardiotoxicity in the Presence of Hyperglycemia in Estrogen-Responsive and Triple-Negative Breast Cancer Cells" International Journal of Molecular Sciences 21, no. 20: 7802. https://doi.org/10.3390/ijms21207802