ArticleBlood2010
Overcoming resistance to histone deacetylase inhibitors in human leukemia with the redox modulating compound β-phenylethyl isothiocyanate.
Article in Blood, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
58 citing papers in PubMed, 97 citations in OpenAlex.
- No evident dose-response relationship between cellular ROS level and its cytotoxicity--a paradoxical issue in ROS-based cancer therapy.Scientific reports · 2014Trial
- Phase II trial of vorinostat with idarubicin and cytarabine for patients with newly diagnosed acute myelogenous leukemia or myelodysplastic syndrome.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2012Trial
- Isothiocyanates as Multi-Target Natural Compounds in Leukemia: Mechanisms, Selectivity, and Therapeutic Potential.International journal of molecular sciences · 2026Review
- STY12, a Novel NQO1/HDAC Dual-Targeting Agent, Exhibits Potent Anti-Pancreatic Cancer Activity by ROS-Mediated DNA Damage.Biomolecules · 2026Article
- HDAC inhibitors in cancer therapy: sensitization mechanisms, combination strategies, and translational challenges.Frontiers in cell and developmental biology · 2026Review
- Molecular, biological characterization and drug sensitivity of chidamide-resistant MCF7 cells.Translational cancer research · 2024Article
- Enhanced efficacy of combined fluzoparib and chidamide targeting in natural killer/T-cell lymphoma.Annals of hematology · 2023Article
- Prospective Epigenetic Actions of Organo-Sulfur Compounds against Cancer: Perspectives and Molecular Mechanisms.Cancers · 2023Review
- Modulation of redox homeostasis: A strategy to overcome cancer drug resistance.Frontiers in pharmacology · 2023Review
- Monitoring Changes in Intracellular Reactive Oxygen Species Levels in Response to Histone Deacetylase Inhibitors.Methods in molecular biology (Clifton, N.J.) · 2023Article
- Improved Anticancer Activities of a New Pentafluorothio-Substituted Vorinostat-Type Histone Deacetylase Inhibitor.Pharmaceuticals (Basel, Switzerland) · 2021Article
- Ferroptosis: At the Crossroad of Gemcitabine Resistance and Tumorigenesis in Pancreatic Cancer.International journal of molecular sciences · 2021Review
- Review
- Mitochondrial metabolism as a target for acute myeloid leukemia treatment.Cancer & metabolism · 2021Review
- Phenethyl Isothiocyanate Enhances the Cytotoxic Effects of PARP Inhibitors in High-Grade Serous Ovarian Cancer Cells.Frontiers in oncology · 2021Article
- ATF3 Coordinates Antitumor Synergy between Epigenetic Drugs and Protein Disulfide Isomerase Inhibitors.Cancer research · 2020Article
- Peroxisome Metabolism in Cancer.Cells · 2020Review
- Combination of Chinese and Western Medicine to Prevent and Reverse Resistance of Cancer Cells to Anticancer Drugs.Chinese journal of integrative medicine · 2020Article
- Article
- Role of HDACs in normal and malignant hematopoiesis.Molecular cancer · 2020Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 2 institutions in 1 country.
Funding
Abstract
Mechanisms of action and resistance of histone deacetylase inhibitors (HDACIs) are not well understood. A gene expression analysis performed in a phase 1 trial of vorinostat in leukemia indicated that overexpression of genes involved in antioxidant defense was associated with clinical resistance. We hypothesized that nonepigenetic mechanisms may be involved in resistance to HDACI therapy in leukemia. Here we confirmed up-regulation of a series of antioxidants in a pan-HDACI-resistant leukemia cell line HL60/LR. Vorinostat induced reactive oxygen species (ROS) through nicotinamide adenine dinucleotide phosphate oxidase in leukemia cells. An increase in ROS resulted in translocation of nuclear factor E2-related factor 2 from cytosol to nucleus, leading to up-regulation of antioxidant genes, including a majority of glutathione-associated enzymes as a cellular protective mechanism. Addition of β-phenylethyl isothiocyanate, a natural compound capable of depleting cellular glutathione, significantly enhanced the cytotoxicity of vorinostat in leukemia cell lines and primary leukemia cells by inhibiting the cytoprotective antioxidant response. These results suggest that ROS plays an important role in action of vorinostat and that combination with a redox-modulating compound increases sensitivity to HDACIs and also overcomes vorinostat resistance. Such a combination strategy may be an effective therapeutic regimen and have potential clinical application in leukemia.
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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.