ArticleLeukemia2008
A novel arsenical has antitumor activity toward As2O3-resistant and MRP1/ABCC1-overexpressing cell lines.
Article in Leukemia, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 18 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
18 citing papers in PubMed, 46 citations in OpenAlex.
- Phase II study of darinaparsin in patients with advanced hepatocellular carcinoma.Investigational new drugs · 2010Trial
- Cytotoxic Effects of Darinaparsin, a Novel Organic Arsenical, against Human Leukemia Cells.International journal of molecular sciences · 2023Article
- Darinaparsin: First Approval.Drugs · 2022Review
- Phase I studies of darinaparsin in patients with relapsed or refractory peripheral T-cell lymphoma: a pooled analysis of two phase I studies conducted in Japan and Korea.Japanese journal of clinical oncology · 2021Article
- Pharmacological GLI2 inhibition prevents myofibroblast cell-cycle progression and reduces kidney fibrosis.The Journal of clinical investigation · 2015Article
- The novel organic arsenical darinaparsin induces MAPK-mediated and SHP1-dependent cell death in T-cell lymphoma and Hodgkin lymphoma cells and human xenograft models.Clinical cancer research : an official journal of the American Association for Cancer Research · 2014Article
- Dimethylarsinothioyl glutathione as a metabolite in human multiple myeloma cell lines upon exposure to Darinaparsin.Chemical research in toxicology · 2014Article
- Glutathione S-conjugates as prodrugs to target drug-resistant tumors.Frontiers in pharmacology · 2014Review
- The novel arsenical Darinaparsin circumvents BRG1-dependent, HO-1-mediated cytoprotection in leukemic cells.Leukemia · 2013Article
- Role of arsenic trioxide in acute promyelocytic leukemia.Current treatment options in oncology · 2013Article
- Darinaparsin: solid tumor hypoxic cytotoxin and radiosensitizer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2012Article
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- Glutathione depletion enhances arsenic trioxide-induced apoptosis in lymphoma cells through mitochondrial-independent mechanisms.British journal of haematology · 2010Article
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- Redox-directed cancer therapeutics: molecular mechanisms and opportunities.Antioxidants & redox signaling · 2009Review
- Effect of arsenic on regulatory T cells.Journal of clinical immunology · 2009Article
- Darinaparsin induces a unique cellular response and is active in an arsenic trioxide-resistant myeloma cell line.Molecular cancer therapeutics · 2009Article
Corrections and comments
- Erratum issued
Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Inorganic arsenic trioxide (As(2)O(3)) is a highly effective treatment for acute promyelocytic leukemia (APL). However, other cancers do not respond well to this form of arsenic at clinically achievable doses. We tested a novel arsenical, S-dimethylarsino-glutathione (darinaparsin) for efficacy in various malignancies in vitro. Darinaparsin is significantly more potent than As(2)O(3) at mediating apoptosis in various malignant cell lines and is highly active against APL cells derived for As(2)O(3) resistance. We provide evidence that darinaparsin triggers apoptosis by inducing signaling pathways that do not completely overlap with As(2)O(3). We show that darinaparsin induces apoptosis and oxidative stress to a greater extent than As(2)O(3), although like As(2)O(3), darinaparsin-induced toxicity is c-Jun NH(2)-terminal kinase-dependent. However, darinaparsin does not induce promyelocytic leukemia/retinoic acid receptor alpha (PML/RAR alpha) degradation or rearrange PML nuclear bodies in APL cells, nor is its toxicity increased by glutathione depletion. Darinaparsin treatment results in higher intracellular arsenic accumulation when compared to As(2)O(3) treatment. This may be explained by our finding that As(2)O(3), but not darinaparsin, is efficiently exported by ABCC1, suggesting increased therapeutic efficacy of darinaparsin in ABCC1-overexpressing tumors. Our studies indicate that darinaparsin efficiently kills tumor cells with increased antioxidant capacity and drug exporters and suggest that darinaparsin may have a broader therapeutic spectrum than As(2)O(3).
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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.