ArticleInternational journal of molecular sciences2020
NLRP3 as Putative Marker of Ipilimumab-Induced Cardiotoxicity in the Presence of Hyperglycemia in Estrogen-Responsive and Triple-Negative Breast Cancer Cells.
Article in International journal of molecular sciences, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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Who cites it
48 citing papers in PubMed, 81 citations in OpenAlex.
- SGLT2 Inhibitor Dapagliflozin Attenuates Cardiomyocyte Injury and Inflammation Induced by PI3Kα-Selective Inhibitor Alpelisib and Fulvestrant Under Hyperglycemia.International journal of molecular sciences · 2026Article
- Targeting NLRP3 Inflammasomes in Myocarditis: Potential Therapeutic Strategies and Clinical Translation.Scientifica · 2026Review
- The impact of SGLT2i on the outcome of advanced lung cancer in patients with diabetes.Frontiers in oncology · 2026Article
- Healthcare Management in Cardio-Oncology, Clinical Strategies and Future Perspectives: A Narrative Review.Healthcare (Basel, Switzerland) · 2025Review
- Hemoglobin glycation index and neutrophil percentage as predictors of congestive heart failure among individuals diagnosed with sepsis: A MIMIC-IV cohort study.Scientific reports · 2025Article
- PCSK9 Inhibitor Inclisiran Attenuates Cardiotoxicity Induced by Sequential Anthracycline and Trastuzumab Exposure via NLRP3 and MyD88 Pathway Inhibition.International journal of molecular sciences · 2025Article
- Unveiling the anticancer potential of SGLT-2 inhibitors: mechanisms and prospects in clinical oncology-a narrative review.European journal of medical research · 2025Review
- In the Era of Cardiovascular-Kidney-Metabolic Syndrome in Cardio-Oncology: From Pathogenesis to Prevention and Therapy.Cancers · 2025Review
- Microbiota-indole-3-propionic acid-heart axis mediates the protection of leflunomide against αPD1-induced cardiotoxicity in mice.Nature communications · 2025Article
- SGLT2 inhibitors for prevention and management of cancer treatment-related cardiovascular toxicity: a review of potential mechanisms and clinical insights.Cardio-oncology (London, England) · 2025Review
- Proarrhythmic Lipid Inflammatory Mediators: Mechanisms in Obesity Arrhythmias.Journal of cellular physiology · 2025Review
- SGLT2 Inhibitors in Combination Therapies for Tumors: A Novel Approach to Synergistic Treatment Strategies.Drug design, development and therapy · 2025Review
- Exploring SGLT2 Inhibitors' Activity in Breast Cancer: An Overview.Current topics in medicinal chemistry · 2025Review
- Increased autophagy activity suppresses hyperglycemia-related colorectal cancer tumorigenesis bothAmerican journal of cancer research · 2025Article
- Research Progress of Regulatory Cell Death in Coronary Microembolization.International journal of medical sciences · 2025Review
- Therapeutic Significance of NLRP3 Inflammasome in Cancer: Friend or Foe?International journal of molecular sciences · 2024Review
- Anti-Diabetic Therapies and Cancer: From Bench to Bedside.Biomolecules · 2024Review
- The Cardioprotective and Anticancer Effects of SGLT2 Inhibitors:JACC. CardioOncology · 2024Review
- Management of Fluoropyrimidine-Induced Cardiac Adverse Outcomes Following Cancer Treatment.Cardiovascular toxicology · 2024Review
- Coexistence of Left Atrial Tumor and Lung Cancer-The Key Role of an Individualized Approach.Diagnostics (Basel, Switzerland) · 2024Article
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
Abstract
Hyperglycemia, obesity and metabolic syndrome are negative prognostic factors in breast cancer patients. Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment, achieving unprecedented efficacy in multiple malignancies. However, ICIs are associated with immune-related adverse events involving cardiotoxicity. We aimed to study if hyperglycemia could affect ipilimumab-induced anticancer efficacy and enhance its cardiotoxicity. Human cardiomyocytes and estrogen-responsive and triple-negative breast cancer cells (MCF-7 and MDA-MB-231 cell lines) were exposed to ipilimumab under high glucose (25 mM); low glucose (5.5 mM); high glucose and co-administration of SGLT-2 inhibitor (empagliflozin); shifting from high glucose to low glucose. Study of cell viability and the expression of new putative biomarkers of cardiotoxicity and resistance to ICIs (NLRP3, MyD88, cytokines) were quantified through ELISA (Cayman Chemical) methods. Hyperglycemia during treatment with ipilimumab increased cardiotoxicity and reduced mortality of breast cancer cells in a manner that is sensitive to NLRP3. Notably, treatment with ipilimumab and empagliflozin under high glucose or shifting from high glucose to low glucose reduced significantly the magnitude of the effects, increasing responsiveness to ipilimumab and reducing cardiotoxicity. To our knowledge, this is the first evidence that hyperglycemia exacerbates ipilimumab-induced cardiotoxicity and decreases its anticancer efficacy in MCF-7 and MDA-MB-231 cells. This study sets the stage for further tests on other breast cancer cell lines and primary cardiomyocytes and for preclinical trials in mice aimed to decrease glucose through nutritional interventions or administration of gliflozines during treatment with ipilimumab.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.