title: Guggulsterone, a plant-derived inhibitor of NF-TB, suppresses CDX2 and COX-2 expression and reduces the viability of esophageal adenocarcinoma cells.
abstract: OBJECTIVE
  Induction by bile acid of caudal type homeobox 2 (CDX2) and cyclooxygenase-2 (COX-2) expression via nuclear factor-κB (NF-κB) activation is a critical event in the development of Barrett's esophagus (BE) and esophageal adenocarcinoma (EAC). Guggulsterone (GS) is a plant sterol that inhibits NF-κB activity. Here, we evaluated whether GS has either or both chemopreventive or therapeutic effects against EAC.
  
  
  METHODS
  Two EAC cells lines were treated with deoxycholic acid (DCA) in the presence of GS or vehicle. The levels of transcription and translation of IκBα, CDX2, and COX-2 were determined. Prostaglandin E2 (PGE2) levels, cell viability, and cell cycle distribution were assessed as well.
  
  
  RESULTS
  GS inhibited DCA-induced IκBα phosphorylation. GS and the NF-κB inhibitor BAY11-7085 suppressed DCA-induced CDX2 and COX-2 expression in EAC cells. GS also suppressed basal transcription levels of CDX2 and COX-2 and reduced constitutive synthesis of COX-2 and PGE2. Further, GS reduced the viability of EAC cells, increased their numbers in the apoptotic sub-G1 fraction.
  
  
  CONCLUSIONS
  GS suppressed DCA-induced and NF-κB-dependent activation of CDX2 and COX-2 expression. Further, GS also reduced the viability of EAC cells. GS may serve as candidate for preventing and treating EAC and BE.
authors.affiliation: Department of Gastroenterology, Iwata City Hospital, Iwata, Japan.
authors.forename: Takanori
authors.initials: T
authors.lastname: Yamada
authors.forename: Satoshi
authors.initials: S
authors.lastname: Osawa
authors.forename: Mutsuhiro
authors.initials: M
authors.lastname: Ikuma
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Kajimura
authors.forename: Mitsushige
authors.initials: M
authors.lastname: Sugimoto
authors.forename: Takahisa
authors.initials: T
authors.lastname: Furuta
authors.forename: Moriya
authors.initials: M
authors.lastname: Iwaizumi
authors.forename: Ken
authors.initials: K
authors.lastname: Sugimoto
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control*; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001471:Barrett Esophagus / Q000378:metabolism / Q000473:pathology; D000071616:CDX2 Transcription Factor; D002460:Cell Line; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002756:Cholagogues and Choleretics / Q000494:pharmacology; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D003840:Deoxycholic Acid / Q000494:pharmacology; D015232:Dinoprostone / Q000096:biosynthesis; D004354:Drug Screening Assays, Antitumor; D004938:Esophageal Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control*; D018398:Homeodomain Proteins / Q000378:metabolism*; D006801:Humans; D020672:I-kappa B Proteins / Q000378:metabolism; D016328:NF-kappa B / Q000187:drug effects*; D009363:Neoplasm Proteins / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D011282:Pregnenediones / Q000494:pharmacology*
chemical_list: D016588:Anticarcinogenic Agents; D000071616:CDX2 Transcription Factor; C491270:CDX2 protein, human; D002756:Cholagogues and Choleretics; D018398:Homeodomain Proteins; C083487:I kappa B beta protein; D020672:I-kappa B Proteins; D016328:NF-kappa B; D009363:Neoplasm Proteins; D011282:Pregnenediones; D003840:Deoxycholic Acid; C023617:pregna-4,17-diene-3,16-dione; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D015232:Dinoprostone