Supplementary Material for: Guggulsterone, a Plant-Derived Inhibitor of NF-TB, Suppresses CDX2 and COX-2 Expression and Reduces the Viability of Esophageal Adenocarcinoma Cells

Background/Aims: Induction by bile acid of caudal type homeobox 2 (CDX2) and cyclooxygenase-2 (COX-2) expression via nuclear factor-TB (NF-TB) 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-TB 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 ITBE, 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 ITBE phosphorylation. GS and the NF-TB 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. Conclusion: GS suppressed DCA-induced and NF-TB-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. i 2014 S. Karger AG, Basel