title: Violaceols function as actin inhibitors inducing cell shape elongation in fibroblast cells.
abstract: Violaceol-I and -II were isolated from a fractionated library of marine-derived fungal metabolites. These compounds increased the calcium ion concentration inside the cell and caused F-actin aggregation in rat fibroblast 3Y1 cells within 3 h resulting in cell shape elongation. Calcium chelator BAPTA-AM (1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid tetrakis (acetoxymethyl ester) inhibited violaceol-I and -II induced F-actin aggregation in 3Y1 cells, and hence violaceol-I and -II act in a calcium dependent manner. Violaceol-I and -II inhibited G-actin polymerization in vitro in a dose-dependent manner and strongly associated with G-actin, at dissociation equilibrium constants of 1.44 × 10(-8) M and 2.52 × 10(-9) M respectively. Here we report the identification of a novel function of violaceol-I and -II as actin inhibitors. Violaceol-I and -II induced cell shape elongation through F-actin aggregation in 3Y1 fibroblasts. These compounds may give researchers new insights into the role of actin in tumorigenesis and lead to the development of additional anti-tumor drugs.
authors.affiliation: Chemical Biology Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), 30 Yeongudanji-ro, Ochang-eup, Cheongwon-gun, Chungbuk 363-883, Korea.
authors.forename: Yukihiro
authors.initials: Y
authors.lastname: Asami
authors.forename: Jae-Hyuk
authors.initials: JH
authors.lastname: Jang
authors.forename: Hyuncheol
authors.initials: H
authors.lastname: Oh
authors.forename: Jae Hak
authors.initials: JH
authors.lastname: Sohn
authors.forename: Jong Won
authors.initials: JW
authors.lastname: Kim
authors.forename: Dong Oh
authors.initials: DO
authors.lastname: Moon
authors.forename: Osong
authors.initials: O
authors.lastname: Kwon
authors.forename: Makoto
authors.initials: M
authors.lastname: Kawatani
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Osada
authors.forename: Bo Yeon
authors.initials: BY
authors.lastname: Kim
authors.forename: Jong Seog
authors.initials: JS
authors.lastname: Ahn
mesh_terms: D000199:Actins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000818:Animals; D059001:Aquatic Organisms / Q000737:chemistry; D001230:Aspergillus / Q000737:chemistry; D002118:Calcium / Q000378:metabolism; D002396:Catechols / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D002460:Cell Line; D048430:Cell Shape / Q000187:drug effects; D003599:Cytoskeleton / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004533:Egtazic Acid / Q000031:analogs & derivatives; D005347:Fibroblasts / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D007700:Kinetics; D058105:Polymerization / Q000187:drug effects; D051381:Rats; D054852:Small Molecule Libraries / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*
chemical_list: D000199:Actins; D002396:Catechols; D054852:Small Molecule Libraries; C070379:1,2-bis(2-aminophenoxy)ethane N,N,N',N'-tetraacetic acid acetoxymethyl ester; D004533:Egtazic Acid; D002118:Calcium