N′-[4-(dipropylamino)benzylidene]-2-hydroxybenzohydrazide is a dynamin GTPase inhibitor that suppresses cancer cell migration and invasion by inhibiting actin polymerization

Hiroshi Yamada, Tadashi Abe, Shun Ai Li, Shota Tago, Peng Huang, Masami Watanabe, Satoru Ikeda, Naohisa Ogo, Akira Asai, Kohji Takei

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Dynasore, a specific dynamin GTPase inhibitor, suppresses lamellipodia formation and cancer cell invasion by destabilizing actin filaments. In search for novel dynamin inhibitors that suppress actin dynamics more efficiently, dynasore analogues were screened. N′-[4-(dipropylamino)benzylidene]-2- hydroxybenzohydrazide (DBHA) markedly reduced in vitro actin polymerization, and dose-dependently inhibited phosphatidylserine-stimulated dynamin GTPase activity. DBHA significantly suppressed both the recruitment of dynamin 2 to the leading edge in U2OS cells and ruffle formation in H1299 cells. Furthermore, DBHA suppressed both the migration and invasion of H1299 cells by approximately 70%. Furthermore, intratumoral DBHA delivery significantly repressed tumor growth. DBHA was much less cytotoxic than dynasore. These results strongly suggest that DBHA inhibits dynamin-dependent actin polymerization by altering the interactions between dynamin and lipid membranes. DBHA and its derivative may be potential candidates for potent anti-cancer drugs.

Original languageEnglish
Pages (from-to)511-517
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume443
Issue number2
DOIs
Publication statusPublished - Jan 10 2014

Keywords

  • Actin cytoskeleton
  • Dynamin
  • Dynasore
  • GTPase
  • Invasion
  • Migration

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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