Cell-morphology profiling of a natural product library identifies bisebromoamide and miuraenamide A as actin filament stabilizers

Eriko Sumiya, Hiroki Shimogawa, Hiroaki Sasaki, Masato Tsutsumi, Keņichi Yoshita, Makoto Ojika, Kiyotake Suenaga, Motonari Uesugi

Research output: Contribution to journalArticle

46 Citations (Scopus)

Abstract

Natural products provide a rich source of biological tools, but elucidating their molecular targets remains challenging. Here we report a cell morphological profiling of a natural product library, which permitted the identification of bisebromoamide and miuraenamide A as actin filament stabilizers. Automated high-content image analysis showed that these two structurally distinct marine natural products induce morphological changes in HeLa cells similar to those induced by known actin-stabilizing compounds. Bisebromoamide and miuraenamide A stabilized actin filaments in vitro, and fluorescein-conjugated bisebromoamide localized specifically to actin filaments in cells. Cell morphological profiling was also used to identify actinstabilizing or -destabilizing natural products from marine sponge extracts, leading to the isolation of pectenotoxin-2 and lyngbyabellin C. Overall, the results demonstrate that high-content imaging of nuclei and cell shapes offers a sensitive and convenient method for detecting and isolating molecules that target actin.

Original languageEnglish
Pages (from-to)425-431
Number of pages7
JournalACS Chemical Biology
Volume6
Issue number5
DOIs
Publication statusPublished - 2011 May 20
Externally publishedYes

Fingerprint

Biological Products
Actin Cytoskeleton
Actins
Cell Nucleus Shape
Porifera
Fluorescein
HeLa Cells
Image analysis
bisebromoamide
miuraenamide A
Imaging techniques
Molecules

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine

Cite this

Cell-morphology profiling of a natural product library identifies bisebromoamide and miuraenamide A as actin filament stabilizers. / Sumiya, Eriko; Shimogawa, Hiroki; Sasaki, Hiroaki; Tsutsumi, Masato; Yoshita, Keņichi; Ojika, Makoto; Suenaga, Kiyotake; Uesugi, Motonari.

In: ACS Chemical Biology, Vol. 6, No. 5, 20.05.2011, p. 425-431.

Research output: Contribution to journalArticle

Sumiya, Eriko ; Shimogawa, Hiroki ; Sasaki, Hiroaki ; Tsutsumi, Masato ; Yoshita, Keņichi ; Ojika, Makoto ; Suenaga, Kiyotake ; Uesugi, Motonari. / Cell-morphology profiling of a natural product library identifies bisebromoamide and miuraenamide A as actin filament stabilizers. In: ACS Chemical Biology. 2011 ; Vol. 6, No. 5. pp. 425-431.
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