| Title: | Novel small-molecule compounds that affect cellular morphogenesis in yeast and mammalian cells |
| Author(s): | Fukunaga T; Nakamura M; Kitagawa T; Watanapokasin R; Hoshida H; Akada R; |
| Address: | "Department of Applied Molecular Bioscience, Yamaguchi University Graduate School of Medicine" |
| Journal Title: | Biosci Biotechnol Biochem |
| ISSN/ISBN: | 1347-6947 (Electronic) 0916-8451 (Linking) |
| Abstract: | "Drugs affecting cellular morphological changes leading to tumor cell migration and invasion are desirable for cancer therapy. In the present study, we screened for small-molecule compounds that affect the cellular morphology of both unicellular yeast and mammalian HEK293 cells to identify drug candidates. The yeast formin protein Bni1 and Src homology 3 (SH3)-pleckstrin homology (PH) domain protein Boi1, which are required for proper morphogenesis, cause growth defects when overexpressed in yeast. Using this system, we screened a chemical library consisting of ???8000 compounds to identify drug candidates that suppress these growth defects. None of the screened compounds induced morphological changes in vegetatively growing yeast cells, but several compounds had inhibitory effects on pheromone-induced projection formation and actin localization, suggesting that these compounds affected a specific stage of morphogenesis. Five of the compounds also induced morphological changes in mammalian HEK293 cells. Among the identified compounds, BTB03156, 2-[(4-chlorophenyl)sulfonyl]-1-methyl-3,5-dinitrobenzene, and BTB02467, 1-[(4-chlorophenyl)sulfonyl]-2-nitro-4-(trifluoromethyl)benzene, although they have similar structures, displayed differing effects on the yeast growth defects caused by latrunculin A, an actin polymerization inhibitor. The chemical library compounds identified using this in vivo screening approach are simple, cell-permeable molecules, and therefore may be useful in the development of therapeutic drugs for cancer metastasis and other actin-related diseases" |
| Keywords: | "Actins/chemistry/*metabolism Adaptor Proteins, Signal Transducing/metabolism Animals Cytoskeleton/drug effects/*metabolism HEK293 Cells Humans Microfilament Proteins/chemistry/*metabolism Morphogenesis/drug effects Saccharomyces cerevisiae Saccharomyces c;" |
| Notes: | "MedlineFukunaga, Tomoaki Nakamura, Mikiko Kitagawa, Takao Watanapokasin, Ramida Hoshida, Hisashi Akada, Rinji eng Research Support, Non-U.S. Gov't England 2013/08/09 Biosci Biotechnol Biochem. 2013; 77(8):1669-76. doi: 10.1271/bbb.130212. Epub 2013 Aug 7" |
