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PALMA NicolÁs Francisco
congresos y reuniones científicas
Título:
DELTA-TOCOTRIENOL ENHANCES THE ANTITUMORAL EFFECTS OF INTERFERON ALPHA THROUGH ROS PRODUCTION AND ERK PATHWAY IN HEPATOCELLULAR CARCINOMA CELLS
Autor/es:
LUCCI, ALVARO; VERA, MARINA C; COMANZO, CARLA G; PALMA NICOLÁS FRANCISCO; FERRETTI, ANABELLA, C; CEBALLOS MANCINI, MARÍA PAULA; QUIROGA, ARIEL DARÍO; ALVAREZ, MARÍA DEL L.; CARRILLO, MARÍA CRISTINA
Reunión:
Congreso; LXVI REUNIÓN ANUAL DE LA SOCIEDAD ARGENTINA DE INVESTIGACIÓN CLÍNICA (SAIC); 2021
Institución organizadora:
Sociedad Argentina de Investigación Clínica
Resumen:
Our group has postulated the supplementation with δ-tocotrienol (E)to interferon alpha (IFN) therapy as a strategy to treat liver cancerbecause we have shown that the combined treatment inhibits cellgrowth and metastatic properties, and increases apoptosis in SKHep-1 (SK) and Huh7 hepatocarcinoma (HCC) cell lines.In this work we explored the signaling pathways involved in the studiedprocesses.Our hypothesis is that reactive oxygen species (ROS) and Erk activationparticipate in the effects produced by E supplementation toIFN therapy.We treated SK and Huh7 cells with 10000 and 20000 U/I IFN, respectively,25 uM E, or the combination of both drugs (IFN-E-group).Also, we used 4 mM N-acetyl cysteine (NAC), a reductor compound,and 5 uM PD98059 (PD), an inhibitor of Erk phosphorylation .Treatmentswere carried out for 72 h. We performed: a) dichlorofluoresceinassay to evaluate ROS production, b) western blot studiesto analyze phospo and total Erk expression, and c) MTT assay todetermine cell viability. Results: IFN-E-group showed a higher increasein ROS production in SK (+500%*) and Huh7 (+350%*) cells,an increase in phospo Erk/ total Erk ratio (SK: +82%* and Huh7:+95%*), and a significant decrease in cell viability (SK:-58%* andHuh7:-52%*). The decreases in viability were parcially restored withPD (IFN-E-PD-group, SK: -25%#, Huh7: -24%#) and with NAC (IFNE-NAC-group, SK: -27%#, Huh7: -15%#). *p