IQUIFIB   02644
INSTITUTO DE QUIMICA Y FISICOQUIMICA BIOLOGICAS "PROF. ALEJANDRO C. PALADINI"
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
DUAL APOPTOTIC/NECROTIC RESPONSE INDUCED BY PHOTODYNAMIC TREATMENT WITH A Zn(II) CATIONIC PHTHALOCYANINE IN MELANOMA CELLS
Autor/es:
MARÍA CECILIA GARCÍA VIOR; LEONOR PATRICIA ROGUIN; FEDERICO VALLI; JULIETA VERÓNICA MARINO
Lugar:
Buenos Aires
Reunión:
Congreso; LXII Reunión Científica Anual de la Sociedad Argentina de Investigación Clínica (SAIC); 2017
Resumen:
Melanoma is an aggressive form of skincarcinoma, highly resistant to traditional therapies. Photodynamic therapy(PDT) is an alternative form of treatment, which combines a photosensitizer,visible light and molecular oxygen to produce reactive oxygen species (ROS)that selectively destroy target cells. In order to find an efficientphotosensitizer to be used in melanoma treatment, we evaluated the effect of asulfur-linked cationic zinc(II) phthalocyanine (Pc13) on a panel of melanomacells (B16F0, B16F10, WM35, M1/15, A375). Incubation withPc13 and irradiation, diminishedcell viability in a concentration and light dose-dependent manner in all thecell lines studied, with IC50 values ranging from 0.20±0.03 mMto 3.60±0.23 mM forB16F0 and A375 cells, respectively. The most sensitive melanoma cells B16F0 were furtheremployed for studying the mechanisms of cell death triggered by Pc13. Acridineorange/ethidium bromide dual staining showed morphological changes characteristicof both necrosis (42±4%) and apoptosis (21±2%) 3h post irradiation of cellstreated with 0.2 µM Pc13. Under these experimental conditions, a significantdecrease in the levels of Bcl-2, Bcl-xL and Bid, and a reduction ofpro-caspase-3 were observed by Western Blot, evidencing an apoptotic response. Furthermore,a time dependent increase of hypodiploid cell population and cell cycle arrestin G0/G1 were assessed by propidium iodide staining and flow cytometryanalysis. In addition, permeabilization of plasma membrane, as sign of necrosis,was evaluated by measuring the release of lactate dehydrogenase (LDH). A lightdose and photosensitizer concentration dependent increase of LDH activity wasdetected in Pc13 treated-cells culture mediums. Taken together,these results indicate that a dual apoptotic and necrotic response is triggeredby Pc13 photoactivation in melanoma cells, suggesting that combined mechanismsof cell death could result in a promising alternative for melanoma treatment.