Document Detail

Susceptibility to cytosine arabinoside (Ara-C)-induced cytotoxicity in human leukemia cell lines.
MedLine Citation:
PMID:  15302096     Owner:  NLM     Status:  MEDLINE    
Cytosine arabinoside (1-beta-d-arabinofuranosylcytosine; Ara-C) is the most important antimetabolite chemotherapeutic drug used for acute leukemia. We examined the difference in susceptibility to Ara-C-induced cell death among a number of typical human leukemia cell lines, NALM-6, MOLT-4, Jurkat, U937 and HL-60. NALM-6, which had a high expression level of p53, a tumor suppressor gene, was most susceptible to Ara-C. U937 and HL-60, with p53-null human leukemia cell lines were little affected by Ara-C. There was not always a correlation between susceptibility and the uptake of Ara-C. The production of reactive oxygen species (ROS) was increased in all leukemia cells. Pifithrin-alpha, a chemical inhibitor of wild-type p53, ameliorated the cytotoxicity of Ara-C in NALM-6 and MOLT-4, but not Jurkat, U937 or HL-60. Our data suggest that the mechanism of Ara-C-induced cell death is a common one, involving an increase in the production of ROS and p53-dependent cell death.
Syu-Ichi Kanno; Ayako Higurashi; Yurie Watanabe; Ai Shouji; Keiko Asou; Masaaki Ishikawa
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Toxicology letters     Volume:  152     ISSN:  0378-4274     ISO Abbreviation:  Toxicol. Lett.     Publication Date:  2004 Sep 
Date Detail:
Created Date:  2004-08-10     Completed Date:  2004-10-21     Revised Date:  2005-11-17    
Medline Journal Info:
Nlm Unique ID:  7709027     Medline TA:  Toxicol Lett     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  149-58     Citation Subset:  IM    
Department of Pharmacology and Toxicology, Cancer Research Institute, Tohoku Pharmaceutical University, 4-4-1 Komatsushima, Aoba-ku, Sendai 981-8558, Japan.
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MeSH Terms
Antimetabolites, Antineoplastic / pharmacology*
Apoptosis / drug effects
Cell Line, Tumor
Cell Nucleus / drug effects,  pathology
Cytarabine / metabolism,  pharmacology*
Dose-Response Relationship, Drug
Gene Expression Regulation, Neoplastic / drug effects*
Genes, p53
Leukemia / drug therapy,  genetics*,  pathology
RNA, Messenger / genetics,  metabolism
Reactive Oxygen Species / metabolism
Reverse Transcriptase Polymerase Chain Reaction
Tumor Suppressor Protein p53 / genetics,  metabolism
Reg. No./Substance:
0/Antimetabolites, Antineoplastic; 0/RNA, Messenger; 0/Reactive Oxygen Species; 0/Tumor Suppressor Protein p53; 147-94-4/Cytarabine

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