Dihydroxy Bile Acids Activate the Transcription of Cyclooxygenase-2

Deoxycholate induces DNA damage and apoptosis in human colon epithelial cells expressing either mutant or wild-type p53

“…Activation of protein kinase C, which is a common event triggered by many tumor promoters, was reported in cultured colon cells that were exposed to deoxycholic acid [12]. Additionally, activation of the transcription factors, AP-1 [13] and NF-κB [14], as well as the NF-κB -responsive cyclooxygenase-2 (COX-2) gene [15], has been reported. Transcriptional activation of COX-2 may promote colon tumor cell growth and proliferation, since expression of COX-2 has been found in colon tumor tissue but not normal colon tissue [16].…”

Induction of retinoic acid receptor-β suppresses cyclooxygenase-2 expression in esophageal cancer cells

“…Previous studies demonstrated that bile acids, potential tumor promoters in gastrointestinal carcinogenesis, can markedly induce both COX-2 mRNA and protein levels in esophageal cancer cell lines (Zhang et al, 1998) and RA can inhibit COX-2 expression (Mestre et al, 1997a,b) but the mechanism is unknown. Therefore, we like to determine whether bile acid-induction of COX-2 and its inhibition by RA are RAR-b dependent, and further investigate the e ect of RARb on COX-2 expression.…”

Bile acids stimulate invasion and haptotaxis in human colorectal cancer cells through activation of multiple oncogenic signaling pathways

“…The AP-1 complex induced by DCA is composed of heterodimers including JunD, Fra-1 and c-Fos, which are actually considered as oncogenic transcription factors implicated in cellular invasion (Hennigan et al, 1994;Kustikova et al, 1998;Ozanne et al, 2000). One of the critical target genes of AP-1 is the cyclooxygenase-2 (COX-2) gene, whose promoter activity and transcription are induced by BA in human colorectal and esophageal adenocarcinoma cells (Zhang et al, 1998;Glinghammer and Rafter, 2001). Induction and constitutive overexpression of COX-2 is strongly implicated in the emergence of human colorectal polyps and in cancer progression, through promotion of cell survival, invasion, and tumor angiogenesis (Fujita et al, 1998;Dannenberg and Zakim, 1999).…”