ArticleLeukemia2003
Glutathione depletion overcomes resistance to arsenic trioxide in arsenic-resistant cell lines.
Article in Leukemia, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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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
45 citing papers in PubMed, 164 citations in OpenAlex.
- Efficacy and safety results with the combination therapy of arsenic trioxide, dexamethasone, and ascorbic acid in multiple myeloma patients: a phase 2 trial.Medical oncology (Northwood, London, England) · 2006Trial
- Metal-dependent regulated cell death: Molecular architecture and translational frontiers.iMeta · 2026Review
- Mechanisms of chemotherapy failure in refractory/relapsed acute myeloid leukemia: the role of cytarabine resistance and mitochondrial metabolism.Cell death & disease · 2025Article
- Additive antitumor effect of arsenic trioxide with exposure to ionizing radiation to human acute promyelocytic leukemia HL‑60 cells.Oncology reports · 2024Article
- An overview of arsenic trioxide-involved combined treatment algorithms for leukemia: basic concepts and clinical implications.Cell death discovery · 2023Review
- The genomic landscape of sensitivity to arsenic trioxide uncovered by genome-wide CRISPR-Cas9 screening.Frontiers in oncology · 2023Article
- Consequences of Arsenic Contamination on Plants and Mycoremediation-Mediated Arsenic Stress Tolerance for Sustainable Agriculture.Plants (Basel, Switzerland) · 2022Review
- An oncogenic enhancer encodes selective selenium dependency in AML.Cell stem cell · 2022Article
- Amplification of oxidative stressNanoscale advances · 2020Article
- Subcellular Organelle Toxicity Caused by Arsenic Nanoparticles in Isolated Rat Hepatocytes.The international journal of occupational and environmental medicine · 2020Article
- p53-TP53-Induced Glycolysis Regulator Mediated Glycolytic Suppression Attenuates DNA Damage and Genomic Instability in Fanconi Anemia Hematopoietic Stem Cells.Stem cells (Dayton, Ohio) · 2019Article
- Article
- Yeast AP-1 like transcription factors (Yap) and stress response: a current overview.Microbial cell (Graz, Austria) · 2019Review
- Intracellular catalase activity instead of glutathione level dominates the resistance of cells to reactive oxygen species.Cell stress & chaperones · 2019Article
- Manipulation of Glucose and Hydroperoxide Metabolism to Improve Radiation Response.Seminars in radiation oncology · 2019Review
- Metabolism-Based Therapeutic Strategies Targeting Cancer Stem Cells.Frontiers in pharmacology · 2019Review
- [Involvement of PML proteins in treatment of acute promyelocytic leukemia with arsenic trioxide].Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences · 2018Review
- Multifactorial Modes of Action of Arsenic Trioxide in Cancer Cells as Analyzed by Classical and Network Pharmacology.Frontiers in pharmacology · 2018Article
- Auranofin radiosensitizes tumor cells through targeting thioredoxin reductase and resulting overproduction of reactive oxygen species.Oncotarget · 2017Article
- Resveratrol protects against arsenic trioxide-induced oxidative damage through maintenance of glutathione homeostasis and inhibition of apoptotic progression.Environmental and molecular mutagenesis · 2015Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Arsenic trioxide (As(2)O(3)) is an effective treatment for acute promyelocytic leukemia (APL), but is less effective against other leukemias. Although the response of APL cells to As(2)O(3) has been linked to degradation of the PML/RARalpha fusion oncoprotein, there is evidence that PML/RARalpha expression is not the only mediator of arsenic sensitivity. Indeed, we found that exogenous expression of PML/RARalpha did not sensitize a non-APL leukemic line to As(2)O(3). To evaluate possible other determinants of sensitivity of leukemic cells to As(2)O(3), we derived two arsenic-resistant NB4 subclones. Despite being approximately 10-fold more resistant to arsenic than their parental cell line, PML/RARalpha protein was still degraded by As(2)O(3) in these cells, providing further evidence that loss of expression of the oncoprotein does not confer arsenic sensitivity. Both arsenic-resistant clones contained high glutathione (GSH) levels, however, and we found that GSH depletion coupled with As(2)O(3) treatment dramatically inhibited their growth. Annexin V-staining and TUNEL analysis confirmed a synergistic induction of apoptosis. In addition, these cells failed to accumulate ROS in response to arsenic treatment, in contrast to their arsenic-sensitive parental cells, unless cotreated with buthionine sulfoximine. While other malignant cells did not show a good correlation between arsenic sensitivity and GSH content, GSH depletion nevertheless sensitized all cell lines examined, regardless of their initial response to arsenic alone. These findings suggest that PML/RARalpha expression is not a determinant of arsenic sensitivity, and further support the coupling of GSH depletion and arsenic treatment as a novel treatment for human malignancies that are unresponsive to arsenic alone.
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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.