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.

Keywords: Actin cytoskeleton; Cytotoxicity; Goniodomin; Hepatocyte; Neuroblastoma; Phycotoxin.