{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T19:02:33Z","timestamp":1790881353765,"version":"4.1.0"},"reference-count":31,"publisher":"BMJ","issue":"12","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Gut"],"accepted":{"date-parts":[[2011,11,23]]},"published-print":{"date-parts":[[2012,12]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>5-aminosalicylic acid (5-ASA) may protect against the development of inflammation-associated colorectal cancer. In vitro data suggest that, in colorectal cancer cells, 5-ASA induces cell cycle arrest, but the molecular mechanism leading to this arrest remains to be determined.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Aim<\/jats:title>\n                    <jats:p>To dissect the signal transduction events that lead to 5-ASA mediated inhibition of proliferation of colorectal cancer cells, focusing on mammalian target of rapamycin (mTOR), a regulator of cell cycle progression.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>The influence of 5-ASA on mTOR signalling was examined in a panel of colorectal cancer cell lines. The effects of 5-ASA on the pathways that control mTOR activity were studied in detail in two different colorectal cancer cell lines, using western blot, siRNA, a phospholipase D (PLD) activity assay, proliferation assays and cell cycle analysis. The phosphorylation status of mTOR and its downstream target, ribosomal protein S6, was studied in colorectal cancers before and after topical 5-ASA treatment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Treatment of colorectal cancer with 5-ASA inhibited mTOR signalling in vitro and in vivo. 5-ASA had no effect on any of the pathways that regulate the activity of the tuberous sclerosis complex in colorectal cancer cells. Both proliferation and mTOR activity depended on PLD, an enzyme that generates phosphatidic acid (PA). 5-ASA treatment inhibited PLD activity and proliferation; these effects could be rescued with exogenous PA.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>5-ASA interferes with proliferation of colorectal cancer cells via inhibition of PLD-dependent generation of PA and loss of mTOR signalling.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/gutjnl-2011-301626","type":"journal-article","created":{"date-parts":[[2011,12,21]],"date-time":"2011-12-21T00:50:19Z","timestamp":1324428619000},"page":"1708-1715","source":"Crossref","is-referenced-by-count":26,"title":["5-aminosalicylic acid inhibits cell cycle progression in a phospholipase D dependent manner in colorectal cancer"],"prefix":"10.1136","volume":"61","author":[{"given":"Bart","family":"Baan","sequence":"first","affiliation":[{"name":"Tytgat Institute for Liver & Intestinal Research, Academic Medical Center, Amsterdam, the Netherlands"},{"name":"Department of Gastroenterology & Hepatology, Leiden University Medical Center, Leiden, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashwin A","family":"Dihal","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology & Hepatology, Leiden University Medical Center, Leiden, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva","family":"Hoff","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology & Hepatology, Leiden University Medical Center, Leiden, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carina L","family":"Bos","sequence":"additional","affiliation":[{"name":"Department of Pathology, VU University Medical Center, Amsterdam, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip W","family":"Voorneveld","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology & Hepatology, Leiden University Medical Center, Leiden, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pim J","family":"Koelink","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology & Hepatology, Leiden University Medical Center, Leiden, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manon E","family":"Wildenberg","sequence":"additional","affiliation":[{"name":"Tytgat Institute for Liver & Intestinal Research, Academic Medical Center, Amsterdam, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vanesa","family":"Muncan","sequence":"additional","affiliation":[{"name":"Tytgat Institute for Liver & Intestinal Research, Academic Medical Center, Amsterdam, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jarom","family":"Heijmans","sequence":"additional","affiliation":[{"name":"Tytgat Institute for Liver & Intestinal Research, Academic Medical Center, Amsterdam, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hein W","family":"Verspaget","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology & Hepatology, Leiden University Medical Center, Leiden, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dick J","family":"Richel","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James C H","family":"Hardwick","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology & Hepatology, Leiden University Medical Center, Leiden, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel W","family":"Hommes","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology & Hepatology, Leiden University Medical Center, Leiden, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maikel P","family":"Peppelenbosch","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gijs R","family":"van den Brink","sequence":"additional","affiliation":[{"name":"Tytgat Institute for Liver & Intestinal Research, Academic Medical Center, Amsterdam, the Netherlands"},{"name":"Department of Gastroenterology & Hepatology, Leiden University Medical Center, Leiden, the Netherlands"},{"name":"Department of Gastroenterology & Hepatology, Academic Medical Center, Amsterdam, the 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