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.


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.


CONCLUSIONS
Guggulsterone may be used as a novel drug to target CdX2 expression in certain gut adenocarcinomas.
Yamada
Takanori
T
First Department of Medicine, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu 431-3192, Japan.
Osawa
Satoshi
S
Hamaya
Yasushi
Y
Furuta
Takahisa
T
Hishida
Akira
A
Kajimura
Masayoshi
M
Ikuma
Mutsuhiro
M
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000473:pathology; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001647:Bile Acids and Salts / Q000037:antagonists & inhibitors*; D000071616:CDX2 Transcription Factor; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D018398:Homeodomain Proteins / Q000037:antagonists & inhibitors*; D006801:Humans; D007414:Intestinal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism; D011282:Pregnenediones / Q000494:pharmacology*; D018160:Receptors, Cytoplasmic and Nuclear / Q000037:antagonists & inhibitors*; D000099150:Receptor, Farnesoid X-Activated
D000972:Antineoplastic Agents, Phytogenic; D001647:Bile Acids and Salts; D000071616:CDX2 Transcription Factor; D018398:Homeodomain Proteins; D016328:NF-kappa B; D011282:Pregnenediones; D018160:Receptors, Cytoplasmic and Nuclear; D000099150:Receptor, Farnesoid X-Activated; C491270:CDX2 protein, human; C023617:pregna-4,17-diene-3,16-dione