ArticlePloS one2014
Arsenic trioxide and resveratrol show synergistic anti-leukemia activity and neutralized cardiotoxicity.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 37 citations in OpenAlex.
- The autophagy switch: A critical determinant of arsenic-induced carcinogenesis and cancer therapy.Toxicology reports · 2026Review
- Pharmacological Foundation and Novel Insights of Resveratrol in Cardiovascular System: A Review.Current cardiology reviews · 2026Review
- Investigating the Mechanisms of Combined Therapy for MCF-7 Breast Cancer Cells Using Arsenic Trioxide and Resveratrol through Network Pharmacology.Phenomics (Cham, Switzerland) · 2025Article
- The Interplay Between Autophagy and Apoptosis in the Mechanisms of Action of Stilbenes in Cancer Cells.Antioxidants (Basel, Switzerland) · 2025Review
- Resveratrol decreases extracellular traps (ETs) in acute promyelocytic leukemia (NB4) cells.PloS one · 2025Article
- An overview of arsenic trioxide-involved combined treatment algorithms for leukemia: basic concepts and clinical implications.Cell death discovery · 2023Review
- Integrative Hematology: State of the Art.International journal of molecular sciences · 2023Review
- Molecular Action of Polyphenols in Leukaemia and Their Therapeutic Potential.International journal of molecular sciences · 2021Review
- Risk Compounds, Preclinical Toxicity Evaluation, and Potential Mechanisms of Chinese Materia Medica-Induced Cardiotoxicity.Frontiers in pharmacology · 2021Review
- Leveraging the Cardio-Protective and Anticancer Properties of Resveratrol in Cardio-Oncology.Nutrients · 2019Review
- Chloroquine exerts antitumor effects on NB4 acute promyelocytic leukemia cells and functions synergistically with arsenic trioxide.Oncology letters · 2018Article
- Review
- Biological effects and epidemiological consequences of arsenic exposure, and reagents that can ameliorate arsenic damageOncotarget · 2017Review
- Tricetin Induces Apoptosis of Human Leukemic HL-60 Cells through a Reactive Oxygen Species-Mediated c-Jun N-Terminal Kinase Activation Pathway.International journal of molecular sciences · 2017Article
- LMTK3 knockdown retards cell growth and invasion and promotes apoptosis in thyroid cancer.Molecular medicine reports · 2017Article
- Deficiency of SUMO-specific protease 1 induces arsenic trioxide-mediated apoptosis by regulating XBP1 activity in human acute promyelocytic leukemia.Oncology letters · 2016Article
- The Coadministration of N-Acetylcysteine Ameliorates the Effects of Arsenic Trioxide on the Male Mouse Genital System.Oxidative medicine and cellular longevity · 2016Article
- Oxidative stress, redox regulation and diseases of cellular differentiation.Biochimica et biophysica acta · 2015Review
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cardiotoxicity is an aggravating side effect of many clinical antineoplastic agents such as arsenic trioxide (As2O3), which is the first-line treatment for acute promyelocytic leukemia (APL). Clinically, drug combination strategies are widely applied for complex disease management. Here, an optimized, cardiac-friendly therapeutic strategy for APL was investigated using a combination of As2O3 and genistein or resveratrol. Potential combinations were explored with respect to their effects on mitochondrial membrane potential, reactive oxygen species, superoxide dismutase activity, autophagy, and apoptosis in both NB4 cells and neonatal rat left ventricular myocytes. All experiments consistently suggested that 5 µM resveratrol remarkably alleviates As2O3-induced cardiotoxicity. To achieve an equivalent effect, a 10-fold dosage of genistein was required, thus highlighting the dose advantage of resveratrol, as poor bioavailability is a common concern for its clinical application. Co-administration of resveratrol substantially amplified the anticancer effect of As2O3 in NB4 cells. Furthermore, resveratrol exacerbated oxidative stress, mitochondrial damage, and apoptosis, thereby reflecting its full range of synergism with As2O3. Addition of 5 µM resveratrol to the single drug formula of As2O3 also further increased the expression of LC3, a marker of cellular autophagy activity, indicating an involvement of autophagy-mediated tumor cell death in the synergistic action. Our results suggest a possible application of an As2O3 and resveratrol combination to treat APL in order to achieve superior therapeutics effects and prevent cardiotoxicity.
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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.