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

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  Publication Details (including relevant citation   information):

  Biochem Pharmacol. 2010 Jun   15;79(12):1759-71. Epub 2010 Feb 24.


  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.

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