The inhibition of protein kinase CK2 activity by the CIGB-300 synthetic peptide impairs the three-dimensional cell growth, Wnt and nuclear factor қB signaling pathways in lung cancer cells.

STÉFANO M. CIRIGLIANO; MARÍA INÉS DÍAZ BESSONE; CAROLINA FLUMIAN; DAMIÁN EMILIO BERARDI; SILVIO E. PEREA; ELISA BAL DE KIER JOFFÉ; HERNÁN FARINA; LAURA TODARO; ALEJANDRO URTREGER

San Diego

Congreso; American Association for Cancer Research Anual Meeting; 2014

American Association for Cancer Research

CK2 is a serine/threonine kinase involved in cell growth, survival and apoptosis. The CIGB-300 is a synthetic peptide capable of binding to CK2 substrates thus preventing the enzyme activity. Previously we have determined that CIGB-300 presented an inhibitory concentration 50 dose (IC50) of 119±2.4 µM in NCI-H125 human lung cancer cells. Throughout an Annexin V-FITC assay we could determine that CIGB-300 is a potent apoptosis inductor since the treatment with this drug for 60 minutes induced apoptosis at a level comparable with that observed with etoposide (10 µM). Concomitantly with cell death induction, we could observe caspase-3 activation and the decreased expression of c-myc and cyclin D1 and D2. In this work we analyzed whether CIGB-300 is able to alter the ability of cells to grow in 3D and to modulate signaling pathways involved in tumor progression. First, we developed stable spheroids of NCI-H125 cells, which were able to grow in culture for at least 14 days. After 5 days of treatment, CIGB-300 induced a significant growth inhibition (median volume: 4.07x107±0.70x107 µm3 in control spheroids vs 2.13x107±0.35x107 µm3 in spheroids treated with the IC50 dose p