The effects of the shellfish toxin
gymnodimine and its analogues (
gymnodimine acetate,
gymnodimine methyl carbonate and gymnodamine) on cellular viability were tested using the Neuro2a
neuroblastoma cell line. Concentrations of toxins up to 10μM had variable effects on reducing cell number as determined using the MTT assay and no effects on the expression of a number of signal transduction
proteins (c-Jun, ATF-2, ATF-3) which are sensitive to cellular stress. However, pre-exposure of Neuro2a cells to 10μM concentrations of toxins for 24h greatly sensitized these cells to the apoptotic effects of another algal toxin,
okadaic acid. These results suggest that
gymnodimine and its analogues sensitize Neuro2a cells to
cytotoxins and raise the possibility that algal blooms involving the production of both
okadaic acid-type molecules and
gymnodimine may generate greater cytotoxicity and pose a greater public health problem. Furthermore, our studies establish the Neuro2a cell line as a potentially high-throughput cellular system sensitive to the pharmacological effects of
gymnodimine and analogues, and as a potential screen for algal-derived toxins.