Lysosomes as the target of yessotoxin in invertebrate and vertebrate cell lines

The toxic effects of the algal polyether phycotoxin yessotoxin (YTX) are studied in the insect fat body IPLB-LdFB and the mouse fibroblast NIH3T3 cell lines. Our experiments confirm the cytotoxic action exerted by the toxin in both insect and mammalian cells, but morphological observations, TUNEL experiments and electrophoretic evalution of DNA integrity failed to evidence a clear pro-apoptotic role for YTX. In both IPLB-LdFB and NIH3T3 cell lines, neutral red and acridine orange stainings, together with evaluation of acid phosphatase activity demonstrate that YTX first damages lysosomal vesicles. This is then followed by a progressive depolymerization of actin microfilaments, as shown by phalloidin fluorescent immunostaining. Overall, our data identify in early lysosomal damage and the subsequent cytoskeletal disruption two common steps related to YTX toxicity towards metazoan cells.