Ponente
Descripción
SticholysinII (StII) is a pore-forming toxin produced by the sea anemone Stichodactyla helianthus that belongs to the actinoporin family. StII forms pores in membranes eventually leading to cell death characterized by calcium release from endoplasmic reticulum (ER) and most probably the induction of ER stress. The aim of this work was to examine the contribution of some intracellular pathways to StII cytotoxicity in murine myeloid P3X63Ag8.653 cells and to evaluate the antitumoral effect of StII in a murine model of a solid tumor. Cytotoxic effect of StII on tumoral cells took place at nanomolar concentrations and led to an increase in cell volume and loss of plasma membrane integrity. Sublytic concentrations of StII on cells induced at, a regulated necrosis characterized by cellular swelling and the involvement of kinases ERK1/2, CaMKII and RIP1 in their cell death mechanism; however, the MAPK p38 was not related to cell death induced by StII. Furthermore, caspases were related to the cell survival. In addition, StII induced release of HMGB1 protein to the extracellular medium and the phosphorylation of the eukaryotic translation factor eIF2α. Antitumor effect in vivo was study in this tumor model in Balb/c mice.The intratumoral administration of StII significantly reduced tumor volume, characterized by extensive areas of necrosis without irreversible adverse effects in animal organs. In conclusion, StII induces a regulated necrosis with the activation of intracellular pathways. The antitumor effect shown in this murine model prompts the study of StII as a promising candidate to be used in antitumoral strategies.
