Faecal unconjugated bile acids in patients with colorectal cancer or polyps.

Imray, Chris; Radley, Stephen; Davis, Andrew; Barker, Geoffrey; Hendrickse, Charles; Donovan, I. A.; Lawson, A. M.; Baker, Peter R.; Neoptolemos, John P.

doi:10.1136/gut.33.9.1239

Cited by 128 publications

(60 citation statements)

References 50 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…One of the most predominant secondary bile acids is deoxycholic acid, which is a cancer-promoting substance as demonstrated in rats by its ability to increase proliferation of colonic crypt cells [8] and potentiate the stomach tumorigenic effect of the chemical carcinogen, N-methyl-N'-nitro-N-nitrosoguanidine [9]. The notion that deoxycholic acid and other secondary bile acids contribute to the development of colon cancer is supported by the finding that elevated levels of secondary bile acids are present in the colon residual fluid or fecal material of human subjects with colon cancer [10].…”

Section: Introductionmentioning

confidence: 54%

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

Powolny

Loo

2001

The International Journal of Biochemistry & Cell Biology

View full text Add to dashboard Cite

Abstract:Diets rich in fat result in higher concentrations of secondary bile acids or their salts in the colon, which may adversely affect cells of the colonic epithelium. Because secondary bile acids are thought to be genotoxic, exposing colon epithelial cells to secondary bile acids may induce DNA damage that might lead to apoptosis. The requirement for the p53 tumor suppressor gene in such events is unknown. In particular, the effects of secondary bile acids on colon epithelial cells having different p53 tumor suppressor gene status have not been examined. Therefore, HCT-116 and HCT-15 human colon adenocarcinoma cells, which express the wild-type and mutant p53 genes, respectively, were exposed to physiological concentrations of deoxycholate. The cells were then analyzed for evidence of DNA damage and apoptosis. After 2 h of incubation with 300 µM deoxycholate, both cell lines had greater levels of single-strand breaks in DNA as assessed by the comet assay. After 6 h of exposure to deoxycholate, HCT-116 and HCT-15 cells showed morphological signs of apoptosis, i.e., membrane blebbing and the presence of apoptotic bodies. Chromatin condensation and fragmentation were also seen after staining DNA with 4',6-diamidino-2-phenylindole. Other apoptotic assays revealed greater binding of annexin V-fluorescein isothiocyanate, as well as greater post-enzymatic labeling with dUTPfluorescein isothiocyanate, by both cell lines exposed to deoxycholate. These data suggest that deoxycholate caused DNA damage in colon epithelial cells that was sufficient to trigger apoptosis in a p53-independent manner.

show abstract

Section: Introductionmentioning

confidence: 54%

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

Powolny

Loo

2001

The International Journal of Biochemistry & Cell Biology

View full text Add to dashboard Cite

show abstract

“…Although the secondary acid compounds may promote the growth of colonic adenomas from which adenocarcinomas may eventually arise (106), epidemiological studies of humans have been conflicting. Some case-control studies have found increased levels of fecal or serum bile acids in patients with colorectal adenomas or cancer (21,22,119,201), whereas others have not (105,170,171). The studies have varied significantly in methodology, choice of controls, the type of bile acid measured (primary, unconjugated, secondary, deoxycholate, etc.…”

Section: Toxic Bacterial Metabolitesmentioning

confidence: 99%

Role of Bacteria in Oncogenesis

2010

View full text Add to dashboard Cite

SUMMARY Although scientific knowledge in viral oncology has exploded in the 20th century, the role of bacteria as mediators of oncogenesis has been less well elucidated. Understanding bacterial carcinogenesis has become increasingly important as a possible means of cancer prevention. This review summarizes clinical, epidemiological, and experimental evidence as well as possible mechanisms of bacterial induction of or protection from malignancy.

show abstract

“…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).…”

mentioning

confidence: 99%

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

Bailey

Zhan

Maru

et al. 2014

American Journal of Physiology-Gastrointestinal and Liver Physi

View full text Add to dashboard Cite

Farnesoid X receptor (FXR) is a bile acid nuclear receptor described through mouse knockout studies as a tumor suppressor for the development of colon adenocarcinomas. This study investigates the regulation of FXR in the development of human colon cancer. We used immunohistochemistry of FXR in normal tissue ( n = 238), polyps ( n = 32), and adenocarcinomas, staged I–IV ( n = 43, 39, 68, and 9), of the colon; RT-quantitative PCR, reverse-phase protein array, and Western blot analysis in 15 colon cancer cell lines; NR1H4 promoter methylation and mRNA expression in colon cancer samples from The Cancer Genome Atlas; DNA methyltransferase inhibition; methyl-DNA immunoprecipitation (MeDIP); bisulfite sequencing; and V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) knockdown assessment to investigate FXR regulation in colon cancer development. Immunohistochemistry and quantitative RT-PCR revealed that expression and function of FXR was reduced in precancerous lesions and silenced in a majority of stage I-IV tumors. FXR expression negatively correlated with phosphatidylinositol-4, 5-bisphosphate 3 kinase signaling and the epithelial-to-mesenchymal transition. The NR1H4 promoter is methylated in ∼12% colon cancer The Cancer Genome Atlas samples, and methylation patterns segregate with tumor subtypes. Inhibition of DNA methylation and KRAS silencing both increased FXR expression. FXR expression is decreased early in human colon cancer progression, and both DNA methylation and KRAS signaling may be contributing factors to FXR silencing. FXR potentially suppresses epithelial-to-mesenchymal transition and other oncogenic signaling cascades, and restoration of FXR activity, by blocking silencing mechanisms or increasing residual FXR activity, represents promising therapeutic options for the treatment of colon cancer.

show abstract

Faecal unconjugated bile acids in patients with colorectal cancer or polyps.

Abstract: The unconjugated faecal bile acid profiles of 14 patients with colorectal cancer, nine patients with polyps and 10 controls were compared using gas

Cited by 128 publications

References 50 publications

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

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

Role of Bacteria in Oncogenesis

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

Contact Info

Product

Resources

About