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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
12
pubmed:dateCreated
2010-4-12
pubmed:abstractText
NO-donating aspirin (NO-ASA, para isomer) has been reported to exhibit strong growth inhibitory effect in Jurkat T-acute lymphoblastic leukemia (T-ALL) cells mediated in part by beta-catenin degradation and caspase activation, but the mechanism(s) still remains unclear. In this study, DNA oligoarrays with 263 genes were used to examine the gene expression profiles relating to stress and drug metabolism, and characterize the stress responses at IC(50) and subIC(50) concentrations of p-NO-ASA (20 and 10microM, respectively) in Jurkat T cells. A total of 22 genes related to heat shock response, apoptosis signaling, detoxifiers and Phase II enzymes, and regulators of cell growth were altered in expression by array analysis based on the expression fold change criteria of > or =1.5-fold or < or =0.65-fold. Real time quantitative RT-PCR confirmed that 20microM p-NO-ASA strongly upregulated the mRNA levels of two heat shock genes HSPA1A (41.5+/-7.01-fold) and HSPA6 (100.4+/-8.11-fold), and FOS (16.2+/-3.2-fold), moderately upregulated HSPH1 (1.71+/-0.43-fold), FMO4 (4.5+/-1.67-fold), CASP9 (1.77+/-0.03-fold), DDIT3 (5.6+/-0.51-fold), and downregulated NF-kappaB1 (0.54+/-0.01-fold) and CCND1 (0.69+/-0.06-fold). Protein levels of Hsp70, the product of HSPA1A, and fos were increased in p-NO-ASA-treated Jurkat T and HT-29 colon cancer cells in a dose-dependent manner. Silencing of Hsp70 enhanced the growth inhibitory effect of p-NO-ASA at low concentrations. The altered gene expression patterns by NO-ASA in Jurkat T cells suggest mechanisms for carcinogen metabolism, anti-proliferative activity and possible chemoprotective activity in T-ALL.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
1873-2968
pubmed:author
pubmed:copyrightInfo
Copyright 2010 Elsevier Inc. All rights reserved.
pubmed:issnType
Electronic
pubmed:day
15
pubmed:volume
79
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1759-71
pubmed:meshHeading
pubmed:year
2010
pubmed:articleTitle
Modulation of stress genes expression profile by nitric oxide-releasing aspirin in Jurkat T leukemia cells.
pubmed:affiliation
Department of Life Sciences, New York Institute of Technology, New York, NY 10023, USA. nnath@nyit.edu
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural