In vitro and in vivo studies of the proapoptotic peptide CIGB-300, an inhibitor of casein kinase 2

BENAVENT ACERO FR; PERERA Y; PEREA SE; ALONSO DF; GOMEZ DE; FARINA HG

Mendoza

Congreso; Reunión Anual de la Sociedad Argentina de Investigaciones en Bioquímica y Biología Molecular; 2012

Sociedad Argentina de Investigaciones en Bioquímica y Biología Molecular

We have previously demonstrated that a proapoptotic cyclic peptide CIGB-300 (P15-Tat) was able to abrogate the CK2-mediated phosphorylation by direct binding to the conserved phosphoacceptor site on their substrates. Previous findings indicated that CIGB-300 inhibits tumor cell proliferation in vitro and reduce tumor growth in cancer animal models. In this work we studied the cellular uptake of CIGB-300 in different sensitive and resistant tumor cells (lung, prostate, leukemia and cervix). We studied the peptide internalization at 37°C and 4°C, and in the presence of metabolic inhibitors to determine the involved mechanism (endocytosis or translocation). We also studied CIGB-300 intracellular trafficking pathways using caveolins and clathrins endocitic markers. Furthermore we determined the degradation mechanism of CIGB-300 in sensitive and resistant cell lines. Finally we evaluated the in vivo anti-angiogenic activity of the peptide in a Matrigel tumor model. CIGB-300 showed an inhibition of blood vessel formation. Altogether, our data shows that CK2 inhibitor peptide differentially affects different tumor cells by either an increase income of the peptide into the cells or by the differences in the intracellular CIGB-300 half-life. Also, these results provide information about how the CIGB-300 would exert its antitumor action by inhibiting tumor angiogenesis.