Abstract 5008: The acetylenic tricyclic bis(cyanoeneone), TBE-31 inhibits non-small cell lung cancer cell migration through direct binding with actin

Abstract

Abstract During metastasis tumor cells undergo epithelial to mesenchymal transition (EMT), where cell-cell junctions dissolve and actin stress fibers are formed. This transition unmasks the migratory and invasive potential of the tumor cells. Here we show that the tricyclic compound TBE-31 binds to purified actin as well as actin from cell lysates. Furthermore, TBE-31 inhibits linear and branched actin polymerization in vitro as well as stress fiber formation in fibroblasts. We also observed that TBE-31 inhibits stress fiber formation in non-small lung cancer cells during TGFβ-dependent EMT. Interestingly, TBE-31 does not interfere with TGFβ-dependent signaling or changes in E- and N-cadherin protein levels during EMT. Finally, we observed that TBE-31 inhibits non-small cell lung tumor cell migration. Our results suggest that TBE-31 targets linear actin polymerization to alter cell morphology and inhibit cell migration. Citation Format: Eddie Chan, Akira Saito, Tadashi Honda, John Di Guglielmo. The acetylenic tricyclic bis(cyanoeneone), TBE-31 inhibits non-small cell lung cancer cell migration through direct binding with actin. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 5008. doi:10.1158/1538-7445.AM2014-5008