VII Simposio Internacional de Ciencias Farmacéuticas 2019 "VII SICF" -VII Simposio "Diseño, Obtención y Desarrollo de Fármacos"

VII Simposio Internacional de Ciencias Farmacéuticas 2019

VII SICF

VII Simposio "Diseño, Obtención y Desarrollo de Fármacos"

EFFECTS IN VITRO AND IN VIVO OF STII: A NATURAL COMPOUND WITH ANTITUMORAL PROPERTIES

Resumen [ES]

SticholysinII (StII) is a protein purified from the sea anemone Stichodactyla helianthus. Based on its ability to form pores in membranes, we evaluated their effects in vitro and in vivo in tumor cells in order to study the antitumor properties of this toxin. In order to understand the cell pathways triggered upon membrane destabilization by StII, we have examined the mechanisms that mediate its cytotoxicity on tumor cells. StII's action on L1210, Raji, X63, B16, A549 tumor cells leads to an increase in cell volume and the release of cytoplasmic components. In the sticholysin-treated cells, an activation of MAPKinases ERK1/2 and p38 were observed. Furthermore, KN62, an inhibitor of CaMKII and Necrostatin, a potent necroptosis inhibitor reduced the cytotoxic activity of StII. Additionally, the integrity of actin cytoskeleton seems to be crucial to pore- formation, probably due to its involvement in the stabilization of the multimeric structure of StII. Combination of toxin with doxorubicin and vincristine provoked the potentiation on chemotherapeutic cytotoxicity. Anti-tumor effect in vivo was study in a subcutaneous X63 tumor model in Balb/c mice. The intra-tumoral injection of StII significantly reduced the tumor volume and the histopathological analysis not showed systemic toxicity. In summary, StII induces cell death by regulated necrosis that depends of the intracellular signalization via MAPKinases and CaMKII. The anti-tumor effect in vivo without systemic toxicity suggests a new antitumoral compound.

Resumen [EN]

SticholysinII (StII) is a protein purified from the sea anemone Stichodactyla helianthus. Based on its ability to form pores in membranes, we evaluated their effects in vitro and in vivo in tumor cells in order to study the antitumor properties of this toxin. In order to understand the cell pathways triggered upon membrane destabilization by StII, we have examined the mechanisms that mediate its cytotoxicity on tumor cells. StII's action on L1210, Raji, X63, B16, A549 tumor cells leads to an increase in cell volume and the release of cytoplasmic components. In the sticholysin-treated cells, an activation of MAPKinases ERK1/2 and p38 were observed. Furthermore, KN62, an inhibitor of CaMKII and Necrostatin, a potent necroptosis inhibitor reduced the cytotoxic activity of StII. Additionally, the integrity of actin cytoskeleton seems to be crucial to pore- formation, probably due to its involvement in the stabilization of the multimeric structure of StII. Combination of toxin with doxorubicin and vincristine provoked the potentiation on chemotherapeutic cytotoxicity. Anti-tumor effect in vivo was study in a subcutaneous X63 tumor model in Balb/c mice. The intra-tumoral injection of StII significantly reduced the tumor volume and the histopathological analysis not showed systemic toxicity. In summary, StII induces cell death by regulated necrosis that depends of the intracellular signalization via MAPKinases and CaMKII. The anti-tumor effect in vivo without systemic toxicity suggests a new antitumoral compound.

Sobre el ponente

Carmen de los Ángeles Soto Febles

Carmen de los Ángeles Soto Febles

Universidad de La Habana Flag of Cuba
Información Práctica
English (US)
No definido
30 minutos
No definido
Autores
Lic. lena de león esperon
Dr. carlos álvarez valcárcel
Dra. ana m. hernández vázquez
Dr. rancés blanco santana
Carmen de los Ángeles Soto Febles
MsC. Juan Carlos Rodríguez Cava
Palabras clave
actinoporins
cancer
cell death
pore forming toxins