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

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47 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

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ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine

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