Induction of spermidine/spermine N1-acetyltransferase (SSAT) by aspirin in Caco-2 colon cancer cells

Biochem J. 2006 Feb 15;394(Pt 1):317-24. doi: 10.1042/BJ20051298.


Epidemiological, experimental and clinical results suggest that aspirin and other NSAIDs (non-steroidal anti-inflammatory drugs) inhibit the development of colon cancer. It has been shown that the NSAID sulindac induces apoptosis and suppresses carcinogenesis, in part, by a mechanism leading to the transcriptional activation of the gene encoding SSAT (spermidine/spermine N1-acetyltransferase), a rate-limiting enzyme in polyamine catabolism. In the present study, we show that a variety of NSAIDs, including aspirin, sulindac, ibuprofen and indomethacin, can induce SSAT gene expression in Caco-2 cells. Aspirin, at physiological concentrations, can induce SSAT mRNA via transcriptional initiation mechanisms. This induction leads to increased SSAT protein levels and enzyme activity. Promoter deletion analysis of the 5' SSAT promoter-flanking region led to the identification of two NF-kappaB (nuclear factor kappaB) response elements. Electrophoretic mobility-shift assays showed binding of NF-kappaB complexes at these sequences after aspirin treatment. Aspirin treatment led to the activation of NF-kappaB signalling and increased binding at these NF-kappaB sites in the SSAT promoter, hence providing a potential mechanism for the induction of SSAT by aspirin in these cells. Aspirin-induced SSAT ultimately leads to a decrease in cellular polyamine content, which has been associated with decreased carcinogenesis. These results suggest that activation of SSAT by aspirin and different NSAIDs may be a common property of NSAIDs that plays an important role in their chemopreventive actions in colorectal cancer.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetyltransferases / biosynthesis*
  • Acetyltransferases / genetics*
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
  • Aspirin / pharmacology*
  • Aspirin / therapeutic use
  • Caco-2 Cells
  • Colonic Neoplasms / enzymology*
  • Colonic Neoplasms / genetics*
  • Colonic Neoplasms / pathology
  • Colonic Neoplasms / prevention & control
  • Dose-Response Relationship, Drug
  • Enzyme Induction / drug effects
  • Humans
  • NF-kappa B / metabolism
  • Peroxisome Proliferator-Activated Receptors / metabolism
  • Promoter Regions, Genetic / genetics
  • Protein Binding
  • Response Elements / genetics


  • Anti-Inflammatory Agents, Non-Steroidal
  • NF-kappa B
  • Peroxisome Proliferator-Activated Receptors
  • Acetyltransferases
  • diamine N-acetyltransferase
  • Aspirin