Colonic luminal contents induce cyclooxygenase 2 transcription in human colon carcinoma cells

Background & Aims: Evidence is accumulating that inhibitors of cyclooxygena se (COX)-2 activity are useful for preventing human colon cancer. Therefore , it is important to determine whether agents in the colonic luminal conten ts can influence the transcriptional regulation of COX-2 in colonic cells. Methods: Transient transfections were performed, using a human COX-2 promot er-luciferase construct, in HCT 116 cells, and the effects of pure luminal compounds and components of fecal water, the fecal fraction in direct conta ct with the colonocytes, on luciferase activity studied. Results: The lumin al compounds deoxycholate, chenodeoxycholate, and butyrate all induced COX- 2 promoter activity in HCT 116 cells. Lipid extracts of human fecal water a lso induced promoter activity in these cells, and the extent of induction v aried between individuals. Induction of COX-2 promoter activity by the lipi d 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 bn COX-2 promoter activity. Conclusions: Components in the luminal contents can effect COX-2 transcription and may influence colonic tumor dev elopment. Available data suggest that the responsible components are under dietary influence.