CIGB-300 treatment in lung cáncer cells: effect on NF-KB inhibition and penetration in 3D spheroids

CIRIGLIANO SM; DÍAZ BESSONE; FLUMIAN C; BERARDI D; PEREA S; BAL DE KIER JOFFÉ; FARINA H; TODARO L; URTREGER A

Bariloche

Simposio; Third South American Symposium in Signal and Molecular Medicine ? SISTAM 2015; 2015

SISTAM

Protein kinase CK2 is a serine-threonine kinase involved in gene expression, chromatin remodeling, cell growth, survival, angiogenesis, and protection from apoptosis. Furthermore, the deregulation of the expression levels and the activity of the CK2 holoenzyme were increased from three to five times in various types of cancers, and was directly associated with tumor development. Overall, this has led to focus attention on the potential of CK2 as a target for cancer treatment. CIGB-300 is a cyclic peptide, which is capable of impairs the activity of the CK2 enzyme by binding to the conserved acidic phosphoaceptor domain of the substrates. In previous works, we showed the proapoptotic and antiproliferative effect of CIGB-300 in different tumor models. In murine and human tumors derived from cervix cancer the CIGB-300 demonstrated a significant antitumor effect. Antiangiogenic properties of CIGB-300 were studied in vitro and in vivo, the peptide alter and inhibit different events that take place in normal endothelial cells HUVEC and decreased the vessels development in CAMs model. In this work the therapeutic action mechanism of CIGB-300 was evaluated in murine (3LL) and human (H-125) lung cancer cells. Exposure of tumor cells to CIGB-300 significantly inhibited cell adhesion, migration and invasion. Moreover, CIGB-300 decreases the proliferation of lung cancer cells, and promotes the nucleolar disruption with the consequent induction of apoptosis. Using different animal models we analyze the antitumor, antimetastatic and anti-angiogenic effect of CIGB-300 by systemic administration. Daily i.v. for five consecutive days with a well-tolerated dose of CIGB-300 (10 mg/kg/day) significantly reduced the ability of 3LL cells to implant and grow in lungs of syngeneic C57/BL6 mice (p