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-kappaB (NF-kappaB) 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 microM. Guggulsterone (up to 5 microM) did not affect cell viability or the cell cycle and did not attenuate bile acid-induced or constitutive NF-kappaB activation. CONCLUSION: Guggulsterone may be used as a novel drug to target CdX2 expression in certain gut adenocarcinomas.
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-kappaB (NF-kappaB) 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 microM. Guggulsterone (up to 5 microM) did not affect cell viability or the cell cycle and did not attenuate bile acid-induced or constitutive NF-kappaB activation. CONCLUSION:Guggulsterone may be used as a novel drug to target CdX2 expression in certain gut adenocarcinomas.
Authors: Eun Sun Jang; Jung-Hwan Yoon; Sung-Hee Lee; Soo-Mi Lee; Jeong-Hoon Lee; Su Jong Yu; Yoon Jun Kim; Hyo-Suk Lee; Chung Yong Kim Journal: J Cancer Res Clin Oncol Date: 2013-11-27 Impact factor: 4.553