title: N'-[4-(dipropylamino)benzylidene]-2-hydroxybenzohydrazide is a dynamin GTPase inhibitor that suppresses cancer cell migration and invasion by inhibiting actin polymerization.
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.
authors: Department of Neuroscience, Okayama University, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1, Shikata-Cho, Kita-ku, Okayama 700-8558, Japan; CREST, JST, 2-5-1, Shikata-Cho, Kita-ku, Okayama 700-8558, Japan. Electronic address: hiroyama@md.okayama-u.ac.jp.
authors: Hiroshi
authors: H
authors: Yamada
authors: Department of Neuroscience, Okayama University, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1, Shikata-Cho, Kita-ku, Okayama 700-8558, Japan; CREST, JST, 2-5-1, Shikata-Cho, Kita-ku, Okayama 700-8558, Japan.
authors: Tadashi
authors: T
authors: Abe
authors: Department of Urology, Okayama University, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1, Shikata-Cho, Kita-ku, Okayama 700-8558, Japan.
authors: Shun-Ai
authors: SA
authors: Li
authors: Department of Neuroscience, Okayama University, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1, Shikata-Cho, Kita-ku, Okayama 700-8558, Japan.
authors: Shota
authors: S
authors: Tago
authors: Department of Urology, Okayama University, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1, Shikata-Cho, Kita-ku, Okayama 700-8558, Japan.
authors: Peng
authors: P
authors: Huang
authors: Department of Urology, Okayama University, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1, Shikata-Cho, Kita-ku, Okayama 700-8558, Japan.
authors: Masami
authors: M
authors: Watanabe
authors: Department of Medical Technology, Graduate School of Health Sciences, Okayama University, 2-5-1, Shikata-Cho, Kita-ku, Okayama 700-8558, Japan.
authors: Satoru
authors: S
authors: Ikeda
authors: Center for Drug Discovery, Graduate School of Pharmaceutical Sciences, University of Shizuoka, 52-1, Yada, Suruga-ku, Shizuoka 422-8526, Japan.
authors: Naohisa
authors: N
authors: Ogo
authors: Center for Drug Discovery, Graduate School of Pharmaceutical Sciences, University of Shizuoka, 52-1, Yada, Suruga-ku, Shizuoka 422-8526, Japan.
authors: Akira
authors: A
authors: Asai
authors: Department of Neuroscience, Okayama University, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1, Shikata-Cho, Kita-ku, Okayama 700-8558, Japan; CREST, JST, 2-5-1, Shikata-Cho, Kita-ku, Okayama 700-8558, Japan.
authors: Kohji
authors: K
authors: Takei
mesh_terms: D000199:Actins / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D019281:Dimerization; D034281:Dynamins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D006835:Hydrazones / Q000008:administration & dosage*; D009361:Neoplasm Invasiveness; D009374:Neoplasms, Experimental / Q000378:metabolism* / Q000473:pathology*
chemical_list: D000199:Actins; D006835:Hydrazones; C511794:N'-(3,4-dihydroxybenzylidene)-3-hydroxy-2-naphthahydrazide; D034281:Dynamins
keywords: Actin cytoskeleton; Dynamin; Dynasore; GTPase; Invasion; Migration