Document Detail

Arsenic trioxide and ascorbic acid demonstrate promising activity against primary human CLL cells in vitro.
MedLine Citation:
PMID:  20171736     Owner:  NLM     Status:  MEDLINE    
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.
Sabyasachi Biswas; Xiaobin Zhao; Andrew P Mone; Xiaokui Mo; Melissa Vargo; David Jarjoura; John C Byrd; Natarajan Muthusamy
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2010-02-19
Journal Detail:
Title:  Leukemia research     Volume:  34     ISSN:  1873-5835     ISO Abbreviation:  Leuk. Res.     Publication Date:  2010 Jul 
Date Detail:
Created Date:  2010-05-24     Completed Date:  2010-06-14     Revised Date:  2014-09-17    
Medline Journal Info:
Nlm Unique ID:  7706787     Medline TA:  Leuk Res     Country:  England    
Other Details:
Languages:  eng     Pagination:  925-31     Citation Subset:  IM    
Copyright Information:
Copyright 2010 Elsevier Ltd. All rights reserved.
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MeSH Terms
Amino Acid Chloromethyl Ketones / pharmacology
Amitrole / pharmacology
Antibodies, Monoclonal / pharmacology
Antibodies, Monoclonal, Humanized
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
Leukemia, Lymphocytic, Chronic, B-Cell / pathology*
Neoplasm Proteins / physiology
Oxidants / pharmacology
Oxidative Stress / drug effects
Oxides / pharmacology*
Reactive Oxygen Species / metabolism
Grant Support
P01 CA095426/CA/NCI NIH HHS; P01 CA95426/CA/NCI NIH HHS; R01 CA102504/CA/NCI NIH HHS
Reg. No./Substance:
0/Amino Acid Chloromethyl Ketones; 0/Antibodies, Monoclonal; 0/Antibodies, Monoclonal, Humanized; 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; 5072-26-4/Buthionine Sulfoximine; EC; EC 3.4.-/Cysteine Proteases; GAN16C9B8O/Glutathione; PQ6CK8PD0R/Ascorbic Acid; ZF80H5GXUF/Amitrole

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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