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: Eddie Chan, Akira Saito, Tadashi Honda, Gianni M Di Guglielmo
• Journal: Cancer prevention research (Philadelphia, Pa.) (Cancer Prev Res (Phila)) Vol. 7 Issue 7 Pg. 727-37 (Jul 2014) ISSN: 1940-6215 [Electronic] United States
• PMID: 24806663 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: ©2014 American Association for Cancer Research.

Chemical References

• Actins
• Cadherins
• Phenanthrenes
• TBE 31
• Transforming Growth Factor beta

Topics

• Actins (metabolism)
• Adenocarcinoma (drug therapy, metabolism, pathology)
• Apoptosis (drug effects)
• Blotting, Western
• Cadherins (metabolism)
• Carcinoma, Non-Small-Cell Lung (drug therapy, metabolism, pathology)
• Cell Movement (drug effects)
• Cell Proliferation (drug effects)
• Cells, Cultured
• Epithelial-Mesenchymal Transition (drug effects)
• Fibroblasts (drug effects, metabolism, pathology)
• Humans
• Immunoprecipitation
• Lung Neoplasms (drug therapy, metabolism, pathology)
• Microscopy, Fluorescence
• Phenanthrenes (pharmacology)
• Stress Fibers
• Transforming Growth Factor beta (metabolism)