Publication:
Novel small-molecule compounds that affect cellular morphogenesis in yeast and mammalian cells

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Issued Date

2013

Resource Type

Article

File Type

application/pdf

ISSN

9168451

DOI

10.1271/bbb.130212

Other identifier(s)

2-s2.0-84883718770

Rights Holder(s)

มหาวิทยาลัยศรีนครินทรวิโรฒ

Bibliographic Citation

Bioscience, Biotechnology and Biochemistry. Vol 77, No.8 (2013), p.1669-1676

Suggested Citation

Fukunaga T., Nakamura M., Kitagawa T., Watanapokasin R., Hoshida H., Akada R. Novel small-molecule compounds that affect cellular morphogenesis in yeast and mammalian cells. Bioscience, Biotechnology and Biochemistry. Vol 77, No.8 (2013), p.1669-1676. doi:10.1271/bbb.130212 Retrieved from: https://hdl.handle.net/20.500.14740/6551

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.

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 actinrelated diseases.

Subject(s)

Actin polymerization
 Bni1
 Boi1
 Formin
 Pleckstrin homology domains
 Cells
 Cytology
 Defects
 Diagnosis
 Mammals
 Molecules
 Morphology
 Polymerization
 Yeast
 Proteins
 Actin
 Actin binding protein
 Bni1 protein, S cerevisiae
 BOI1 protein, S cerevisiae
 Saccharomyces cerevisiae protein
 Signal transducing adaptor protein
 Animal
 Article
 Cell strain HEK293
 Chemistry
 Cytoskeleton
 Drug effect
 Human
 Metabolism
 Molecular library
 Morphogenesis
 Saccharomyces cerevisiae
 Actins
 Adaptor Proteins, Signal Transducing
 Animals
 Cytoskeleton
 HEK293 Cells
 Humans
 Microfilament Proteins
 Morphogenesis
 Saccharomyces cerevisiae
 Saccharomyces cerevisiae Proteins
 Small Molecule Libraries

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URI

https://hdl.handle.net/20.500.14740/6551

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Scopus: Year 1983-2021

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