Cytotoxicity of goniodomin A and B in non contractile cells

Begoña Espiña, Eva Cagide, M. Carmen Louzao, Natalia Vilariño, Mercedes R. Vieytes, Yoshiyuki Takeda, Makoto Sasaki, Luis M. Botana

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    8 Citations (Scopus)

    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.

    Original languageEnglish
    Pages (from-to)10-20
    Number of pages11
    JournalToxicology Letters
    Volume250-251
    DOIs
    Publication statusPublished - 2016 May 27

    Keywords

    • Actin cytoskeleton
    • Cytotoxicity
    • Goniodomin
    • Hepatocyte
    • Neuroblastoma
    • Phycotoxin

    ASJC Scopus subject areas

    • Toxicology

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  • Cite this

    Espiña, B., Cagide, E., Louzao, M. C., Vilariño, N., Vieytes, M. R., Takeda, Y., Sasaki, M., & Botana, L. M. (2016). Cytotoxicity of goniodomin A and B in non contractile cells. Toxicology Letters, 250-251, 10-20. https://doi.org/10.1016/j.toxlet.2016.04.001