Modulation of stress genes expression profile by nitric oxide-releasing aspirin in Jurkat T leukemia cells

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 IC50 and subIC(50) concentrations of p-NO-ASA (20 and 10 mu M, 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 >= 1.5-fold or <= 0.65-fold. Real time quantitative RT-PCR confirmed that 20 mu M p-NO-ASA strongly upregulated the mRNP, 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-kappa B1 (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 land 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. (C) 2010 Elsevier Inc. All rights reserved.

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