+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

Ursodeoxycholic acid inhibits interleukin 1 beta [corrected] and deoxycholic acid-induced activation of NF-kappaB and AP-1 in human colon cancer cells



Ursodeoxycholic acid inhibits interleukin 1 beta [corrected] and deoxycholic acid-induced activation of NF-kappaB and AP-1 in human colon cancer cells



International Journal of Cancer 118(3): 532-539



Deoxycholic acid (DCA) has been implicated in colorectal carcinogenesis in humans with effects on proliferation and apoptosis, mediated at least in part by activation of transcription factors nuclear factor kappa B (NF-kappaB), activator protein 1 (AP-1) and protein kinase C (PKC) enzymes. Ursodeoxycholic acid (UDCA) is reported to reduce the frequency of colonic carcinogenesis in ulcerative colitis patients. Hence, we postulated that it might differ from DCA in its regulation of these transcription factors. The aim of the study was to determine effects of DCA and UDCA on NF-kappaB and AP-1 activation and explore its relationship to PKC. Human colonic tumour cell lines HCT116 were treated with DCA, UDCA, alone or pretreated with UDCA followed by DCA or IL-1beta. In other experiments, cells were pretreated with PKC inhibitors and then stimulated with DCA and IL-1beta or PMA. Gel shift assays were performed on nuclear extracts of the cells for NF-kappaB and AP-1 analysis. Western blot analyses and immunofluorescence were performed for Rel A (p65) and IkappaB-alpha levels on the treated cells. DCA increased NF-kappaB and AP-1 DNA binding. UDCA did not increase DNA binding of NF-kappaB and AP-1 and UDCA pretreatment inhibited DCA-induced NF-kappaB and AP-1 DNA binding. PKC inhibitors blocked DCA-induced NF-kappaB and AP-1 activation. These results were validated by Western blot analysis for RelA and IkappaB-alpha. In conclusion, UDCA did not induce NF-kappaB and AP-1 DNA binding but also blocked DCA-induced NF-kappaB and AP-1 activation. These findings suggest a possible mechanistic role for UDCA in blocking pathways thought to be involved in colon carcinogenesis.

Please choose payment method:






(PDF emailed within 0-6 h: $19.90)

Accession: 050902008

Download citation: RISBibTeXText

PMID: 16106402

DOI: 10.1002/ijc.21365


Related references

Differential effects of tumour promoting bile acid deoxycholic acid and chemoprotective ursodeoxycholic acid on protein kinase c beta 1, epsilon and delta and transcription factors, nf kappab and ap 1 in human colon cancer cells. Digestive Disease Week Abstracts & Itinerary Planner : Abstract No S992, 2003

Chronic but not acute conjugated linoleic acid treatment inhibits deoxycholic acid-induced protein kinase C and nuclear factor-kappaB activation in human colorectal cancer cells. European Journal of Cancer Prevention 15(2): 125-133, 2006

Ursodeoxycholic acid (UDCA) can inhibit deoxycholic acid (DCA)-induced apoptosis via modulation of EGFR/Raf-1/ERK signaling in human colon cancer cells. Journal of Nutrition 134(2): 483-486, 2004

Ursodeoxycholic acid protects colon cancer HCT116 cells from deoxycholic acid-induced apoptosis by inhibiting apoptosome formation. Nutrition and Cancer 64(4): 617-626, 2012

Ursodeoxycholic Acid (Udca) Can Inhibit Deoxycholic Acid (Dca)-induced Apoptosis via Modulation of Egfr/Raf-1/Erk Signaling in Human Colon Cancer Cells1. The Journal of Nutrition 134(2): 483-486, 2004

Vitamin C inhibits nuclear factor-kappaB activation in oesophageal cells exposed to deoxycholic acid-potential cancer preventative treatment in patients with Barretts metaplasia. Gut 53(Suppl 3): A63, 2004

Differential regulation of EGFR-MAPK signaling by deoxycholic acid (DCA) and ursodeoxycholic acid (UDCA) in colon cancer. Digestive Diseases and Sciences 59(10): 2367-2380, 2014

W1976 Opposing Effects of Deoxycholic Acid and Ursodeoxycholic Acid On Golgi Structure; Implications for Colon Cancer Progression. Gastroenterology 134(4): A-746, 2008

Chemoprotective ursodeoxycholic acid, but not chemopromotional cholic acid, prevents the activation of PKC-beta-2 and PKC-zeta in the azoxymethane model of colon cancer. Gastroenterology 108(4 Suppl. ): A550, 1995

Apoptosis induced by deoxycholic acid, unconjugated bilirubin and amyloid beta-peptide reflects mitochondrial perturbation which may be inhibited by ursodeoxycholic acid. Journal of Hepatology 32(Suppl. 2): 40, 2000

Ursodeoxycholic acid inhibits Ras mutations, wild-type Ras activation, and cyclooxygenase-2 expression in colon cancer. Cancer Research 63(13): 3517-3523, 2003

Beta-Lapachone-induced apoptosis is associated with activation of caspase-3 and inactivation of NF-kappaB in human colon cancer HCT-116 cells. Anti-Cancer Drugs 14(10): 845-850, 2003

Opposing effects of bile acids deoxycholic acid and ursodeoxycholic acid on signal transduction pathways in oesophageal cancer cells. European Journal of Cancer Prevention 25(5): 368-379, 2016

Estrogen responsive DNA binding ring finger protein is induced by deoxycholic acid but not by ursodeoxycholic acid treatment in colonic carcinoma cells. Gastroenterology 112(4 Suppl. ): A587, 1997

Bile acids deoxycholic acid and ursodeoxycholic acid differentially regulate human β-defensin-1 and -2 secretion by colonic epithelial cells. Faseb Journal 31(9): 3848-3857, 2017