ArticleClinical cancer research : an official journal of the American Association for Cancer Research2014
Decitabine induces delayed reactive oxygen species (ROS) accumulation in leukemia cells and induces the expression of ROS generating enzymes.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2014. 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, 84 citations in OpenAlex.
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- Oxidative Stress and Mitochondrial Dysfunction in Myelodysplastic Syndrome: Roles in Development, Diagnosis, Prognosis, and Treatment.International journal of molecular sciences · 2025Review
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- Oxidative stress is two-sided in the treatment of acute myeloid leukemia.Cancer medicine · 2024Review
- Role of reactive oxygen species in myelodysplastic syndromes.Cellular & molecular biology letters · 2024Review
- Synergistic cytotoxicity of decitabine and YM155 in leukemia cells through upregulation of SLC35F2 and suppression of MCL1 and survivin expression.Apoptosis : an international journal on programmed cell death · 2024Article
- Inhibiting glycosphingolipids alleviates cardiac hypertrophy by reducing reactive oxygen species and restoring autophagic homeostasis.Frontiers in pharmacology · 2024Article
- High glucose promotes apoptosis and autophagy of MC3T3-E1 osteoblasts.Archives of medical science : AMS · 2023Article
- Combined scRNAseq and Bulk RNAseq Analysis to Reveal the Dual Roles of Oxidative Stress-Related Genes in Acute Myeloid Leukemia.Oxidative medicine and cellular longevity · 2023Article
- Inhibitory effect and related mechanism of decitabine combined with gemcitabine on proliferation of NK/T cell lymphoma cells.Frontiers in pharmacology · 2023Article
- Modulation of the activity of histone lysine methyltransferases and demethylases by curcumin analog in leukaemia cells.Journal of cellular and molecular medicine · 2022Article
- Research progress on pharmacological effects and new dosage forms of baicalin.Veterinary medicine and science · 2022Review
- Anticancer effect of selenium/chitosan/polyethylene glycol/allyl isothiocyanate nanocomposites against diethylnitrosamine-induced liver cancer in rats.Saudi journal of biological sciences · 2022Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
purposeAzanucleoside DNA methyltransferase (DNMT) inhibitors are currently approved by the U.S. Food and Drug Administration for treatment of myelodysplastic syndrome. The relative contributions of DNMT inhibition and other off-target effects to their clinical efficacy remain unclear. Data correlating DNA methylation reversal and clinical response have been conflicting. Consequently, it is necessary to investigate so-called off-target effects and their impact on cell survival and differentiation. EXPERIMENTAL
designFlow cytometry was used for cell cycle, apoptosis, and reactive oxygen species (ROS) accumulation analysis. Gene expression analysis was performed using real-time PCR. DNA methylation was detected by methylation-specific PCR. Mitochondrial membrane potential was analyzed using JC-1 dye staining. Western blotting was used for quantitative protein expression analysis.
results5-Aza-2'-deoxycytidine (DAC) induced cell-cycle arrest and apoptosis in leukemia cells. p53 expression was dispensable for DAC-induced apoptosis. DAC induced delayed ROS accumulation in leukemia cells but not in solid tumor cells and p53 expression was dispensable for ROS increase. ROS increase was deoxycytidine kinase dependent, indicating that incorporation of DAC into nuclear DNA is required for ROS generation. ROS accumulation by DAC was caspase-independent and mediated the dissipation of the mitochondrial membrane potential. Concordantly, ROS scavengers diminished DAC-induced apoptosis. DAC induced the expression of different NADPH oxidase isoforms and upregulated Nox4 protein expression in an ATM-dependent manner, indicating the involvement of DNA damage signaling in Nox4 upregulation.
conclusionThese data highlight the importance of mechanisms other than DNA cytosine demethylation in modulating gene expression and suggest investigating the relevance of ROS accumulation to the clinical activity of DAC.
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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.