Guggulsterone suppresses bile acid-induced and constitutive caudal-related homeobox 2 expression in gut-derived adenocarcinoma cells.

Background: Guggulsterone, a plant polyphenol guggulipid, has several antitumour effects and acts as an antagonist for the farnesoid X receptor. Although bile acids induce caudal-related homeobox 2 (CdX2), a transcription factor essential for intestinal development and gut tumourigenesis, the effects of guggulsterone on regulation of CdX2 in the gut are unknown. Materials and Methods: Regulation of CdX2 expression by treatment with bile acids and/or guggulsterone was analysed by immunoblot analysis in human gut-derived adenocarcinoma, Bic-1 cells. Nuclear factor-kappa B (NF-kappa B) activity and the cell cycle distribution were also examined. Results: Chenodeoxycholic acid and deoxycholic acid increased CdX2 expression in Bic-1 cells. Guggulsterone reduced bile acid-induced and constitutive CdX2 expression at 5 mu M. Guggulsterone (up to 5 mu M) did not affect cell viability or the cell cycle and did not attenuate bile acid-induced or constitutive NF-kappa B activation. Conclusion: Guggulsterone may be used as a novel drug to target CdX2 expression in certain gut adenocarcinomas.