title: Cytotoxicity of goniodomin A and B in non contractile cells.
abstract: Goniodomin A is a phycotoxin produced by the dinoflagellates Alexandrium hiranoi (formerly Goniodoma pseudogoniaulax) and Alexandrium monilatum. This polyether macrolide exerts a potent antifungal effect and disturbs the actomyosin ATPase activity and the F-actin meshwork in diverse cell types. Goniodomin B is a fused acetal isomer isolated with goniodomin A with unknown activity. Histopathological changes induced by goniodomin A postulated hepatocytes as target cells. In this study both compounds induce a time and concentration dependent fall in the viability of Clone 9 rat hepatocytes. Furthermore, for both compounds, primary rat hepatocytes are almost 10 folds less sensitive than Clone 9 cells. Goniodomin A is highly effective in the nanomolar range while micromolar concentrations of goniodomin B are necessary to observe cytoxicity. Additionally, goniodomin A induced a significant increase in the F-actin and decrease in the G-actin content of Clone 9 cells but did not change the actin of primary cultured hepatocytes. However, goniodomin B could not exert significant alterations in the cytoskeleton of neither cell type. Futhermore goniodomin A as well as goniodomin B are cytotoxic to excitable cells. Both analogues triggered a time dependent decrease on viability in BE(2)-M17 human neuroblastoma cells. In this cell model goniodomin A increased the intracellular calcium and depolarized cells. We conclude that goniodomins A and B are biologically active molecules in hepatocytes and also in excitable cells BE(2)-M17. However, the analogue goniodomin B, whose activity is described in this work for the first time, is a much less potent compound.
authors.affiliation: Departamento de Farmacologia, Facultad de Veterinaria, Universidad de Santiago de Compostela, 27002 Lugo, Spain. Electronic address: begona.espina@inl.int.
authors.forename: Begoña
authors.initials: B
authors.lastname: Espiña
authors.affiliation: Departamento de Farmacologia, Facultad de Veterinaria, Universidad de Santiago de Compostela, 27002 Lugo, Spain. Electronic address: evacagide@cifga.es.
authors.forename: Eva
authors.initials: E
authors.lastname: Cagide
authors.affiliation: Departamento de Farmacologia, Facultad de Veterinaria, Universidad de Santiago de Compostela, 27002 Lugo, Spain. Electronic address: mcarmen.louzao@usc.es.
authors.forename: M Carmen
authors.initials: MC
authors.lastname: Louzao
authors.affiliation: Departamento de Farmacologia, Facultad de Veterinaria, Universidad de Santiago de Compostela, 27002 Lugo, Spain. Electronic address: natalia.vilarino@usc.es.
authors.forename: Natalia
authors.initials: N
authors.lastname: Vilariño
authors.affiliation: Departamento de Fisiologia Animal, Facultad de Veterinaria, Universidad de Santiago de Compostela, 27002 Lugo, Spain. Electronic address: mmercedes.rodriguez@usc.es.
authors.forename: Mercedes R
authors.initials: MR
authors.lastname: Vieytes
authors.affiliation: Laboratory of Biostructural Chemistry, Graduate School of Life Sciences, Tohoku University, 2-1-1 Katahira, Aoba-ku, Sendai 980-8577, Japan. Electronic address: yoshiyuki.takeda@takeda.com.
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Takeda
authors.affiliation: Laboratory of Biostructural Chemistry, Graduate School of Life Sciences, Tohoku University, 2-1-1 Katahira, Aoba-ku, Sendai 980-8577, Japan. Electronic address: masasaki@m.tohoku.ac.jp.
authors.forename: Makoto
authors.initials: M
authors.lastname: Sasaki
authors.affiliation: Departamento de Farmacologia, Facultad de Veterinaria, Universidad de Santiago de Compostela, 27002 Lugo, Spain. Electronic address: Luis.Botana@usc.es.
authors.forename: Luis M
authors.initials: LM
authors.lastname: Botana
mesh_terms: D008841:Actin Cytoskeleton / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004987:Ethers / Q000633:toxicity*; D022781:Hepatocytes / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D018942:Macrolides / Q000633:toxicity*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009447:Neuroblastoma / Q000378:metabolism / Q000473:pathology; D061251:Primary Cell Culture; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
chemical_list: D004987:Ethers; D018942:Macrolides; C059668:goniodomin A; D002118:Calcium
keywords: Actin cytoskeleton; Cytotoxicity; Goniodomin; Hepatocyte; Neuroblastoma; Phycotoxin