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

Naveen Babbar, Eugene W. Gerner, Robert A. Casero

Research output: Contribution to journalArticlepeer-review

Abstract

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 N 1-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-κB (nuclear factor κB) response elements. Electrophoretic mobility-shift assays showed binding of NF-κB complexes at these sequences after aspirin treatment. Aspirin treatment led to the activation of NF-κB signalling and increased binding at these NF-κB sites in the SSAT promoter, hence providing a potential mechanism for the induction of SSAT by aspirin in these cells. Aspirininduced 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.

Original languageEnglish (US)
Pages (from-to)317-324
Number of pages8
JournalBiochemical Journal
Volume394
Issue number1
DOIs
StatePublished - Feb 15 2006

Keywords

  • Aspirin
  • Caco-2 colon cancer cell
  • Non-steroidal anti-inflammatory drugs (NSAIDs)
  • Nuclear factor κB (NF-κB)
  • Polyamine
  • Spermidine/spermine N-acetyltransferase

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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