IQUIFIB   02644
INSTITUTO DE QUIMICA Y FISICOQUIMICA BIOLOGICAS "PROF. ALEJANDRO C. PALADINI"
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
PHOTOTOXIC ACTION OF A ZINC(II) CATIONIC PHTHALOCYANINE ON MURINE MELANOMA B16F0 CELLS
Autor/es:
NICOLÁS CHIARANTE; JULIETA VERÓNICA MARINO; FEDERICO VALLI; MARÍA CECILIA GARCÍA VIOR; JOSEFINA AWRUCH; LEONOR PATRICIA ROGUIN
Lugar:
Mar del Plata
Reunión:
Congreso; LXI Reunión Científica Anual de la Sociedad Argentina de Investigación Clínica (SAIC); 2016
Resumen:
Malignant melanoma is the most aggressive form of skin carcinoma,which possesses fast proliferation rate and highlyinvasive characteristics. Phthalocyanines (Pcs) are synthetic photosensitizerswith potential application in photodynamic therapy. In order to find anefficient photosensitizer to be used in melanoma treatment, we study the effectof a sulfur-linked cationic zinc(II) phthalocyanine named Pc13 on murinemelanoma B16F0 cells. While no citotoxicity was observed by MTT assay whencells were incubated with Pc13 in the dark, cell viability diminished in aconcentration-dependent manner upon exposure to a light dose of 9.2 Jcm-2,being the IC50 value of 0.19 ± 0.09 µM. The production of ROS inPc13-loaded cells was demonstrated immediately after irradiation with the probeDCFH-DA. When cells were pretreated with 5 mM of the antioxidant trolox, cell viabilitywas completely recovered. A cytosolic localization of Pc13, that emits a redfluorescence after exciting at 633 nm, was revealed by confocal microscopy. Thepresence of picnotic nuclei in Pc13-treated cells was also detected after Hoechststaining. In order to elucidate the induction of the mitochondrial pathway,Pc13-treated cells were irradiated and incubated with DiOC6 probe. Mitochondrialdepolarization was observed 1 h post irradiation by fluorescence microscopy andflow cytometry. We also detected lower levels of poly-ADPribose-polymerase(PARP), a caspase-3 substrate involved in DNA repair. In addition, a rapidphosphorylation of p38, JNK and Erk1/2 MAPK, anda decrease of p-Akt levels were observed after irradiation of Pc13-loadedcells. Taken together, these results indicate that the phototoxic effectexerted by Pc13 on melanoma B16F0 cells is mediated by the formation of ROS andthe induction of an apoptotic response characterized by mitochondrialdepolarization, PARP cleavage and nuclear shrinkage. The role of kinases in thephototoxic action will be further investigated.