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

<b><i>Background/Aims:</i></b> 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. <b><i>Methods:</i></b> Two EAC cells lines were treated with deoxycholic acid (DCA) in the presence of GS or vehicle. The levels of transcription and translation of <i>ITBE</i>, <i>CDX2</i>, and <i>COX-2</i> were determined. Prostaglandin E<sub>2</sub> (PGE<sub>2</sub>) levels, cell viability, and cell cycle distribution were assessed as well. <b><i>Results:</i></b> GS inhibited DCA-induced ITBE phosphorylation. GS and the NF-TB inhibitor BAY11-7085 suppressed DCA-induced <i>CDX2</i> and <i>COX-2</i> expression in EAC cells. GS also suppressed basal transcription levels of <i>CDX2</i> and <i>COX-2</i> and reduced constitutive synthesis of COX-2 and PGE<sub>2</sub>. Further, GS reduced the viability of EAC cells, increased their numbers in the apoptotic sub-G1 fraction. <b><i>Conclusion:</i></b> GS suppressed DCA-induced and NF-TB-dependent activation of <i>CDX2</i> and <i>COX-2</i> 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