Abstract 1548: The effects of synthetic triterpenoids on GSK3β and focal adhesions

Abstract Synthetic triterpenoids are a class of anti-cancer compounds that are efficacious in targeting multiple cellular functions including apoptosis, growth inhibition, anti-inflammation and cytoprotection in both cell culture and animal tumor models. However, its effects on cell migration, a precursor event to cancer metastasis, remain poorly understood. Previously, we have shown that the methyl ester derivative of 2-cyano-3,12-dioxooleana-1,9-dien-28-oic acid (CDDO-Me) inhibits cell migration. The objective of our current study is to examine in further detail the mechanism by which CDDO-Me blocks cell migration. Using various proteomic approaches as well as affinity pull down assays, Glycogen Synthase Kinase 3 Beta (GSK3β) was identified and confirmed as a triterpenoid-binding protein. Since GSK3β has been shown to be an important regulator of cell adhesion, a process that is intricately connected to cell migration, we hypothesize that CDDO-Me may target GSK3β and affect cell adhesion dynamics to inhibit cell migration. Indeed, we have observed that triterpenoid treated cells have decreased GSK3β activity. We also observed that the size and shape of focal adhesions were altered in the presence of synthetic triterpenoids. The molecular link between synthetic triterpenoids, GSK3β and focal adhesions are currently being investigated to better describe how this promising anti-cancer compound may act via GSK3β to affect focal adhesions and cell migration. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1548. doi:10.1158/1538-7445.AM2011-1548