B Glinghammar1, J Rafter. 1. Department of Medical Nutrition, Karolinska Institutet, Novum, Huddinge, Sweden.
Abstract
BACKGROUND & AIMS: Evidence is accumulating that inhibitors of cyclooxygenase (COX)-2 activity are useful for preventing human colon cancer. Therefore, it is important to determine whether agents in the colonic luminal contents can influence the transcriptional regulation of COX-2 in colonic cells. METHODS: Transient transfections were performed, using a human COX-2 promoter-luciferase construct, in HCT 116 cells, and the effects of pure luminal compounds and components of fecal water, the fecal fraction in direct contact with the colonocytes, on luciferase activity studied. RESULTS: The luminal compounds deoxycholate, chenodeoxycholate, and butyrate all induced COX-2 promoter activity in HCT 116 cells. Lipid extracts of human fecal water also induced promoter activity in these cells, and the extent of induction varied between individuals. Induction of COX-2 promoter activity by the lipid extracts was positively correlated with induction of activator protein 1-dependent gene transcription. Results also indicated that protein kinase C and p38 mitogen-activated protein kinase mediated the effect of the luminal agents on COX-2 promoter activity. CONCLUSIONS: Components in the luminal contents can effect COX-2 transcription and may influence colonic tumor development. Available data suggest that the responsible components are under dietary influence.
BACKGROUND & AIMS: Evidence is accumulating that inhibitors of cyclooxygenase (COX)-2 activity are useful for preventing humancolon cancer. Therefore, it is important to determine whether agents in the colonic luminal contents can influence the transcriptional regulation of COX-2 in colonic cells. METHODS: Transient transfections were performed, using a humanCOX-2 promoter-luciferase construct, in HCT 116 cells, and the effects of pure luminal compounds and components of fecal water, the fecal fraction in direct contact with the colonocytes, on luciferase activity studied. RESULTS: The luminal compounds deoxycholate, chenodeoxycholate, and butyrate all induced COX-2 promoter activity in HCT 116 cells. Lipid extracts of human fecal water also induced promoter activity in these cells, and the extent of induction varied between individuals. Induction of COX-2 promoter activity by the lipid extracts was positively correlated with induction of activator protein 1-dependent gene transcription. Results also indicated that protein kinase C and p38 mitogen-activated protein kinase mediated the effect of the luminal agents on COX-2 promoter activity. CONCLUSIONS: Components in the luminal contents can effect COX-2 transcription and may influence colonic tumor development. Available data suggest that the responsible components are under dietary influence.
Authors: Pieter Friederich; Jelle Verschuur; Bjorn W H van Heumen; Hennie M J Roelofs; Marloes Berkhout; Iris D Nagtegaal; Martijn G H van Oijen; Johannes H J M van Krieken; Wilbert H M Peters; Fokko M Nagengast Journal: Int J Colorectal Dis Date: 2011-01-18 Impact factor: 2.571
Authors: Kristin A Verbeke; Alan R Boobis; Alessandro Chiodini; Christine A Edwards; Anne Franck; Michiel Kleerebezem; Arjen Nauta; Jeroen Raes; Eric A F van Tol; Kieran M Tuohy Journal: Nutr Res Rev Date: 2015-06 Impact factor: 7.800