ArticleCancer chemotherapy and pharmacology2018
Combinatorial effects of histone deacetylase inhibitors (HDACi), vorinostat and entinostat, and adaphostin are characterized by distinct redox alterations.
Article in Cancer chemotherapy and pharmacology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed, 13 citations in OpenAlex.
- Curcumin in High Doses Reverses the UV-B-InducedPharmaceuticals (Basel, Switzerland) · 2026Article
- Adaphostin-induced oxidative stress in oesophageal neuroendocrine carcinoma: a potential therapeutic strategy.Medical oncology (Northwood, London, England) · 2026Article
- Monitoring Changes in Intracellular Reactive Oxygen Species Levels in Response to Histone Deacetylase Inhibitors.Methods in molecular biology (Clifton, N.J.) · 2023Article
- Valproic Acid Inhibits Glioma and Its Mechanisms.Journal of healthcare engineering · 2022Article
- Reactive Oxygen Species-Mediated Mitochondrial Dysfunction Triggers Sodium Valproate-Induced Cytotoxicity in Human Colorectal Adenocarcinoma Cells.Journal of gastrointestinal cancer · 2021Article
- Sodium Valproate, a Histone Deacetylase Inhibitor, Provokes Reactive Oxygen Species-Mediated Cytotoxicity in Human Hepatocellular Carcinoma Cells.Journal of gastrointestinal cancer · 2021Article
- Chidamide-Induced Accumulation of Reactive Oxygen Species Increases Lenalidomide Sensitivity Against Multiple Myeloma Cells.OncoTargets and therapy · 2021Article
- Natural Agents Targeting Mitochondria in Cancer.International journal of molecular sciences · 2020Review
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6 authors at 1 institution in 1 country.
Funding
Abstract
purposeAmongst the epigenetically targeted therapies, targeting of the histone deacetylases (HDACs) has yielded numerous drugs for clinical use in hematological malignancies, but none as yet for acute lymphocytic leukemia (ALL). Single agent activity of HDAC inhibitors (HDACi) has been elusive in ALL, and has prompted study of combinatorial strategies. Because several HDACi raise levels of intracellular oxidative stress, we evaluated combinations of two structurally distinct HDACi with the redox active compound adaphostin in ALL.
methodsThe HDACi vorinostat and entinostat were tested in combination with adaphostin in human ALL cell lines. DNA fragmentation, caspase activation, mitochondrial disruption and levels of intracellular peroxides, superoxide and glutathione were measured in cells treated with the HDACi/adaphostin combinations. Antioxidant blockade of cell death induction and gene expression profiling of cells treated with vorinostat/adaphostin versus entinostat/adaphostin combinations were evaluated.
resultsBoth combinations synergistically induced apoptotic DNA fragmentation, which was preceded by an increase in superoxide levels, a reduction in mitochondrial membrane potential, and an increase in caspase-9 activation. The antioxidant N-acetylcysteine (NAC) blocked superoxide generation and prevented reduction of mitochondrial membrane potential. NAC decreased DNA fragmentation and caspase activity in cells treated with adaphostin and vorinostat, but not in those treated with adaphostin and entinostat. Gene expression arrays revealed differential regulation of several redox genes prior to cell death induction.
conclusionsA redox modulatory agent, adaphostin, enhances efficacy of two HDACi, vorinostat or entinostat, but via different mechanisms indicating a point of divergence in the mechanisms of synergy between the two distinct HDACi and adaphostin.
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