Colonic luminal contents induce cyclooxygenase 2 transcription in human colon carcinoma cells.
OBJECTIVE
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.
Glinghammar
B
B
Department of Medical Nutrition, Karolinska Institutet, Novum, Huddinge, Sweden.
Rafter
J
J
D020148:Butyric Acid / Q000494:pharmacology; D003106:Colon / Q000166:cytology / Q000201:enzymology*; D051546:Cyclooxygenase 2; D003840:Deoxycholic Acid / Q000494:pharmacology*; D003902:Detergents / Q000494:pharmacology*; D005243:Feces / Q000201:enzymology*; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D017930:Genes, Reporter; D019073:HT29 Cells; D006801:Humans; D007527:Isoenzymes / Q000235:genetics*; D008156:Luciferases / Q000235:genetics; D008565:Membrane Proteins; D018809:Proliferating Cell Nuclear Antigen / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000187:drug effects / Q000502:physiology; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis; D014158:Transcription, Genetic / Q000187:drug effects* / Q000502:physiology*; D014162:Transfection; D014867:Water / Q000494:pharmacology
D003902:Detergents; D007527:Isoenzymes; D008565:Membrane Proteins; D018809:Proliferating Cell Nuclear Antigen; D012333:RNA, Messenger; D003840:Deoxycholic Acid; D014867:Water; D020148:Butyric Acid; D008156:Luciferases; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases