The effect of alginates on deoxycholic-acid-induced changes in oesophageal mucosal biology at pH 4.
Long-standing gastro-oesophageal reflux disease (GORD) can give rise to Barrett's oesophagus (BM), a metaplastic condition and precursor to oesophageal adenocarcinoma (AC). Oesophageal cancer was once rare but is now the 5th biggest cancer killer in the U.K. Reflux of bile acids into the oesophagus is implicated in the progression to BM as bile acids at pH 4 have been shown to induce c-myc expression, an oncogene upregulated in BM and AC. In the present study we investigated the role of the biopolymer alginate on bile acid induced molecular changes in oesophageal cell lines. OE21, OE33 and TE-7 oesophageal cell lines were exposed to 100 microM deoxycholic acid at pH 4 in the presence or absence of alginates. Levels of c-myc, E-cadherin, beta-catenin and Tcf signalling were determined by Real-Time PCR, Western blotting, immunofluoresence and reporter assays. All alginates tested were able to prevent the induction of c-myc by acidified deoxycholic acid in vitro. The upstream effects of acidified deoxycholic acid on E-cadherin, beta-catenin and Tcf signalling were also suppressed by alginate. Therefore, we have demonstrated that reflux of bile acids into the oesophagus initiates a potentially damaging molecular cascade of events using an in vitro model and that a biopolymer, alginate, can protect against these effects.
Dettmar
Peter W
PW
Technostics, The Deep Business Centre, Kingston Upon Hull, East Yorkshire, HU1 4BG, UK.
Strugala
Vicki
V
Tselepis
Chris
C
Jankowski
Janusz A
JA
D000464:Alginates / Q000494:pharmacology*; D002294:Carcinoma, Squamous Cell; D002454:Cell Differentiation / Q000187:drug effects; D045744:Cell Line, Tumor; D003840:Deoxycholic Acid / Q000494:pharmacology*; D004938:Esophageal Neoplasms; D004947:Esophagus; D006801:Humans; D006863:Hydrogen-Ion Concentration; D009092:Mucous Membrane / Q000187:drug effects / Q000502:physiology*
D000464:Alginates; D003840:Deoxycholic Acid