ArticleMolecular cancer therapeutics2009
Darinaparsin induces a unique cellular response and is active in an arsenic trioxide-resistant myeloma cell line.
Article in Molecular cancer therapeutics, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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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
24 citing papers in PubMed, 45 citations in OpenAlex.
- Standardization of [F-18]FDG PET/CT for response evaluation by the Radiologic Society of North America-Quantitative Imaging Biomarker Alliance (RSNA-QIBA) profile: preliminary results from the Japan-QIBA (J-QIBA) activities for Asian international multicenter phase II trial.Japanese journal of radiology · 2018Trial
- The arsenic proteome in cancer: Unravelling molecular mechanisms of anticancer drugs.Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry · 2026Review
- Review
- Unveiling the link between arsenic toxicity and diabetes: an in silico exploration into the role of transcription factors.Toxicological research · 2024Article
- Darinaparsin (ZIO-101) enhances the sensitivity of small-cell lung cancer to PARP inhibitors.Acta pharmacologica Sinica · 2023Article
- Cytotoxic Effects of Darinaparsin, a Novel Organic Arsenical, against Human Leukemia Cells.International journal of molecular sciences · 2023Article
- Darinaparsin: First Approval.Drugs · 2022Review
- Advances in glioma-associated oncogene (GLI) inhibitors for cancer therapy.Investigational new drugs · 2022Review
- Association between Arsenic Level, Gene Expression in Asian Population, and In Vitro Carcinogenic Bladder Tumor.Oxidative medicine and cellular longevity · 2022Article
- Multifactorial Modes of Action of Arsenic Trioxide in Cancer Cells as Analyzed by Classical and Network Pharmacology.Frontiers in pharmacology · 2018Article
- Metabolism, toxicity and anticancer activities of arsenic compounds.Oncotarget · 2017Review
- Determination of multiple human arsenic metabolites employing high performance liquid chromatography inductively coupled plasma mass spectrometry.Journal of chromatography. B, Analytical technologies in the biomedical and life sciences · 2016Article
- Hepatic and Nephric NRF2 Pathway Up-Regulation, an Early Antioxidant Response, in Acute Arsenic-Exposed Mice.International journal of environmental research and public health · 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
- Arsenic-mediated activation of the Nrf2-Keap1 antioxidant pathway.Journal of biochemical and molecular toxicology · 2013Review
- Monitoring Response and Resistance to the Novel Arsenical Darinaparsin in an AML Patient.Frontiers in pharmacology · 2013Article
- Darinaparsin: solid tumor hypoxic cytotoxin and radiosensitizer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2012Article
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 1 country.
Funding
Abstract
Here, we report on the organic arsenical darinaparsin (ZIO-101, S-dimethylarsino-glutathione) and its anti-myeloma activity compared with inorganic arsenic trioxide. Darinaparsin induced apoptosis in multiple myeloma cell lines in a dose-dependent manner, and the addition of N-acetylcysteine, which increases intracellular glutathione (GSH), blocked cytotoxicity of both darinaparsin and arsenic trioxide. In contrast to arsenic trioxide, intracellular GSH does not appear to be important for darinaparsin metabolism, as an inhibitor of GSH synthesis, buthionine sulfoximine, had little effect on drug activity. This discrepancy was resolved when we determined the effects of thiols on drug uptake. The addition of exogenous GSH, L-cysteine, or D-cysteine prevented darinaparsin cellular uptake and cell death but had no effect on the uptake or activity of arsenic trioxide, suggesting a difference in the transport mechanism of these two drugs. In addition, gene expression profiling revealed differences in the signaling of protective responses between darinaparsin and arsenic trioxide. Although both arsenicals induced a transient heat shock response, only arsenic trioxide treatment induced transcription of metal response genes and anti-oxidant genes related to the Nrf2-Keap1 pathway. In contrast to the protective responses, both arsenicals induced up-regulation of BH3-only proteins. Moreover, silencing of BH3-only proteins Noxa, Bim, and Bmf protected myeloma cells from darinaparsin-induced cell death. Finally, treatment of an arsenic trioxide-resistant myeloma cell line with darinaparsin resulted in dose-dependent apoptosis, indicating that cross-resistance does not necessarily develop between these two forms of arsenic in multiple myeloma cell lines. These results suggest darinaparsin may be useful as an alternative treatment in arsenic trioxide-resistant hematologic cancers.
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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.