Carcinogenicity of deoxycholate, a secondary bile acid

Abstract

High dietary fat causes increased bile acid secretion into the gastrointestinal tract and is associated with colon cancer. Since the bile acid deoxycholic acid (DOC) is suggested to be important in colon cancer etiology, this study investigated whether DOC, at a high physiologic level, could be a colon carcinogen. Addition of 0.2% DOC for 8–10 months to the diet of 18 wild-type mice induced colonic tumors in 17 mice, including 10 with cancers. Addition of the antioxidant chlorogenic acid at 0.007% to the DOC-supplemented diet significantly reduced tumor formation. These results indicate that a high fat diet in humans, associated with increased risk of colon cancer, may have its carcinogenic potential mediated through the action of bile acids, and that some dietary anti-oxidants may ameliorate this carcinogenicity.

Secondary bile acids effects in colon pathology. Experimental mice study

“…Lesions location in the proximal colon is also reported by Bernstein et al 7 in a study conducted on male mice, which had been fed with a supplement of 0.20% DOC for 10 months. A similar result is described by Prasad et al 13 who described changes like Peyer's hyperplasia plates in the small intestine of female mice.…”

“…High levels of bile acids due to high-fat diets (individuals with a Western-style diet) may act as carcinogens in the development of colon cancer in humans 7 . The function as carcinogenic promoters of these secondary bile acids has been demonstrated in numerous studies, including those of Baijal et al 8 , Seraj et al 9 , Narisawa et al 10 , Reddy et al 11 , Narahari et al 12 and many others, by experiments in which these acids were administrated to lab animals (mice, rats) previously treated with a proved carcinogen.…”

“…Moreover, Bernstein et al 7 published an article to prove the role of deoxycholic acid as carcinogen agent when is administred orally to mice for 8-10 months in an increased concentration of 0.2 %. They proved thus that the presence of this bile acid in the gastrointestinal tract over a long period of time can lead to the occurrence of adenomas and colon carcinomas in mice.…”

FXR silencing in human colon cancer by DNA methylation and KRAS signaling

“…Bile acids (BAs) are amphipathic molecules essential for digestion and absorption of fats. Highfat diet increases BA load in the intestine whereas low dietary fiber prolongs gastrointestinal transit time, thus collectively increasing the level and time of BA exposure (2,33). Although BAs are essential for lipid absorption, high concentration of BAs is linked to increased colon tumorigenesis (2,17,27).…”

“…Highfat diet increases BA load in the intestine whereas low dietary fiber prolongs gastrointestinal transit time, thus collectively increasing the level and time of BA exposure (2,33). Although BAs are essential for lipid absorption, high concentration of BAs is linked to increased colon tumorigenesis (2,17,27). Indeed, patients with colorectal cancer increased fecal BA excretion (11,43).…”