title: The acetylenic tricyclic bis(cyano enone), TBE-31 inhibits non-small cell lung cancer cell migration through direct binding with actin.
abstract: The migratory and invasive potential of the epithelial-derived tumor cells depends on epithelial-to-mesenchymal transition (EMT) as well as the reorganization of the cell cytoskeleton. Here, we show that the tricyclic compound acetylenic tricyclic bis(cyano enone), TBE-31, directly binds to actin and inhibits linear and branched actin polymerization in vitro. Furthermore, we observed that TBE-31 inhibits stress fiber formation in fibroblasts as well as in non-small cell lung cancer cells during TGFβ-dependent EMT. Interestingly, TBE-31 does not interfere with TGFβ-dependent signaling or changes in E-cadherin and N-cadherin protein levels during EMT. Finally, we observed that TBE-31 inhibits fibroblast and non-small cell lung tumor cell migration with an IC50 of 1.0 and 2.5 μmol/L, respectively. Taken together, our results suggest that TBE-31 targets linear actin polymerization to alter cell morphology and inhibit cell migration.
authors.affiliation: Authors' Affiliations: Department of Physiology and Pharmacology, University of Western Ontario, London, Ontario, Canada;
authors.forename: Eddie
authors.initials: E
authors.lastname: Chan
authors.affiliation: Institute of Chemical Biology and Drug Discovery; and.
authors.forename: Akira
authors.initials: A
authors.lastname: Saito
authors.affiliation: Institute of Chemical Biology and Drug Discovery; and Department of Chemistry, Stony Brook University, Stony Brook, New York.
authors.forename: Tadashi
authors.initials: T
authors.lastname: Honda
authors.affiliation: Authors' Affiliations: Department of Physiology and Pharmacology, University of Western Ontario, London, Ontario, Canada; john.diguglielmo@schulich.uwo.ca.
authors.forename: Gianni M
authors.initials: GM
authors.lastname: Di Guglielmo
mesh_terms: D000199:Actins / Q000378:metabolism*; D000230:Adenocarcinoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D015820:Cadherins / Q000378:metabolism; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects*; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D047468:Immunoprecipitation; D008175:Lung Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D008856:Microscopy, Fluorescence; D010616:Phenanthrenes / Q000494:pharmacology*; D022502:Stress Fibers; D016212:Transforming Growth Factor beta / Q000378:metabolism
chemical_list: D000199:Actins; D015820:Cadherins; D010616:Phenanthrenes; C531972:TBE 31; D016212:Transforming Growth Factor beta