{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,23]],"date-time":"2026-02-23T19:46:31Z","timestamp":1771875991089,"version":"3.50.1"},"reference-count":49,"publisher":"Portland Press Ltd.","issue":"1","content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2006,2,15]]},"abstract":"<jats:p>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\u2032 SSAT promoter-flanking region led to the identification of two NF-\u03baB (nuclear factor \u03baB) response elements. Electrophoretic mobility-shift assays showed binding of NF-\u03baB complexes at these sequences after aspirin treatment. Aspirin treatment led to the activation of NF-\u03baB signalling and increased binding at these NF-\u03baB 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.<\/jats:p>","DOI":"10.1042\/bj20051298","type":"journal-article","created":{"date-parts":[[2006,3,2]],"date-time":"2006-03-02T09:17:57Z","timestamp":1141291077000},"page":"317-324","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":85,"title":["Induction of spermidine\/spermine <i>N<\/i>1-acetyltransferase (SSAT) by aspirin in Caco-2 colon cancer cells"],"prefix":"10.1042","volume":"394","author":[{"given":"Naveen","family":"Babbar","sequence":"first","affiliation":[{"name":"The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Johns Hopkins University School of Medicine, Baltimore, MD 21231, U.S.A."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eugene\u00a0W.","family":"Gerner","sequence":"additional","affiliation":[{"name":"Department of Cell Biology and Anatomy, Arizona Cancer Center, University of Arizona, 1515 N. Campbell Ave., P.O. Box 245024, Tucson, AZ 85724, U.S.A."},{"name":"Department of Biochemistry and Molecular Biophysics, Arizona Cancer Center, University of Arizona, 1515 N. Campbell Ave., P.O. Box 245024, Tucson, AZ 85724, U.S.A."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"suffix":"Jr","given":"Robert\u00a0A.","family":"Casero","sequence":"additional","affiliation":[{"name":"The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Johns Hopkins University School of Medicine, Baltimore, MD 21231, U.S.A."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"288","published-online":{"date-parts":[[2006,1,27]]},"reference":[{"key":"2021112213303287300_B1","first-page":"IV12","article-title":"History of aspirin and its mechanism of action","volume":"21","author":"Vane","year":"1990","journal-title":"Stroke"},{"key":"2021112213303287300_B2","first-page":"2909","article-title":"Sulindac sulfone inhibits azoxymethane-induced colon carcinogenesis in rats without reducing prostaglandin levels","volume":"57","author":"Piazza","year":"1997","journal-title":"Cancer Res."},{"key":"2021112213303287300_B3","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1006\/excr.1996.0023","article-title":"Nonsteroidal antiinflammatory drugs inhibit the proliferation of colon adenocarcinoma cells: effects on cell cycle and apoptosis","volume":"222","author":"Shiff","year":"1996","journal-title":"Exp. 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