title: Cell-morphology profiling of a natural product library identifies bisebromoamide and miuraenamide A as actin filament stabilizers.
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 actin-stabilizing 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.
authors.forename: Eriko
authors.initials: E
authors.lastname: Sumiya
authors.forename: Hiroki
authors.initials: H
authors.lastname: Shimogawa
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Sasaki
authors.forename: Masato
authors.initials: M
authors.lastname: Tsutsumi
authors.forename: Ken'ichi
authors.initials: K
authors.lastname: Yoshita
authors.forename: Makoto
authors.initials: M
authors.lastname: Ojika
authors.forename: Kiyotake
authors.initials: K
authors.lastname: Suenaga
authors.forename: Motonari
authors.initials: M
authors.lastname: Uesugi
mesh_terms: D008841:Actin Cytoskeleton / Q000187:drug effects*; D001688:Biological Products / Q000494:pharmacology*; D002467:Cell Nucleus / Q000187:drug effects; D047630:Depsipeptides / Q000494:pharmacology*; D005663:Furans / Q000302:isolation & purification / Q000494:pharmacology; D006801:Humans; D008235:Lyngbya Toxins / Q000494:pharmacology; D018942:Macrolides; D009842:Oligopeptides / Q000494:pharmacology*; D011714:Pyrans / Q000302:isolation & purification / Q000494:pharmacology; D013844:Thiazoles / Q000494:pharmacology; D000095702:Polyether Toxins
chemical_list: D001688:Biological Products; D047630:Depsipeptides; D005663:Furans; D008235:Lyngbya Toxins; D018942:Macrolides; D009842:Oligopeptides; D011714:Pyrans; D013844:Thiazoles; C545819:bisebromoamide; C560796:lyngbyabellin C; C514528:miuraenamide A; C098380:pectenotoxin 2; D000095702:Polyether Toxins