| Arsenic trioxide and ascorbic acid demonstrate promising activity against primary human CLL cells in vitro. | |
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MedLine Citation:
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PMID: 20171736 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The compromised antioxidant defense system in chronic lymphocytic leukemia (CLL) suggested a potential use for reactive oxygen species (ROS) generating arsenic trioxide (ATO) and ascorbic acid. While both ATO and ascorbic acid mediate cytotoxicity in CLL B cells as single agents, the efficacy of ATO is enhanced by ascorbic acid. This effect is dependent on increased ROS accumulation, as pretreatment of B-CLL cells with a glutathione reducing buthionine sulfoximine or catalase inhibiting aminotriazole, enhanced ATO/ascorbic acid-mediated cytotoxicity. Pretreatment with reducing agents such as catalase, or thiol antioxidant, N-acetyl cysteine or GSH also abrogated ATO/ascorbic acid-mediated cytotoxicity. Furthermore, Hu1D10-mediated cell death was enhanced with ATO and ascorbic acid, thus justifying potential combination of ATO/arsenic trioxide therapy with antibodies such as Hu1D10 that also cause accumulation of ROS. |
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Authors:
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Sabyasachi Biswas; Xiaobin Zhao; Andrew P Mone; Xiaokui Mo; Melissa Vargo; David Jarjoura; John C Byrd; Natarajan Muthusamy |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2010-02-19 |
Journal Detail:
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Title: Leukemia research Volume: 34 ISSN: 1873-5835 ISO Abbreviation: Leuk. Res. Publication Date: 2010 Jul |
Date Detail:
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Created Date: 2010-05-24 Completed Date: 2010-06-14 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 7706787 Medline TA: Leuk Res Country: England |
Other Details:
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Languages: eng Pagination: 925-31 Citation Subset: IM |
Copyright Information:
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Copyright 2010 Elsevier Ltd. All rights reserved. |
Affiliation:
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Division of Hematology and Oncology, Department of Internal Medicine, The Ohio State University, Columbus, OH 43210, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Amino Acid Chloromethyl Ketones
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pharmacology Amitrole / pharmacology Antibodies, Monoclonal / pharmacology Arsenicals / pharmacology* Ascorbic Acid / pharmacology* B-Lymphocytes / drug effects, pathology Buthionine Sulfoximine / pharmacology Catalase / antagonists & inhibitors, pharmacology Cell Line, Tumor / drug effects Cysteine Proteases / physiology Cysteine Proteinase Inhibitors / pharmacology Drug Evaluation, Preclinical Drug Synergism Enzyme Activation / drug effects Glutathione / metabolism Humans Leukemia, Lymphocytic, Chronic, B-Cell / pathology* Neoplasm Proteins / physiology Oxidants / pharmacology Oxidative Stress / drug effects Oxides / pharmacology* Reactive Oxygen Species / metabolism |
| Grant Support | |
ID/Acronym/Agency:
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P01 CA95426/CA/NCI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Amino Acid Chloromethyl Ketones; 0/Antibodies, Monoclonal; 0/Arsenicals; 0/Cysteine Proteinase Inhibitors; 0/Neoplasm Proteins; 0/Oxidants; 0/Oxides; 0/Reactive Oxygen Species; 0/apolizumab; 0/benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone; 1327-53-3/arsenic trioxide; 50-81-7/Ascorbic Acid; 5072-26-4/Buthionine Sulfoximine; 61-82-5/Amitrole; 70-18-8/Glutathione; EC 1.11.1.6/Catalase; EC 3.4.-/Cysteine Proteases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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