Effect of the CIGB-300 synthetic peptide in the modulation of signaling pathways involved with malignant progression of human and murine lung tumors

URTREGER; CIRIGLIANO; DIAZ BESSONE; FLUMIAN; BERARDI; BAL DE KIER JOFFE; TODARO; FARINA

Washington

Congreso; 104 Annual Meeting of the American Association for Cancer Research; 2013

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. In this work we have studied the effect of IGBC-300 on several signaling pathways involved in tumor progression, cell cycle, apoptosis and biological effects associated metastatic dissemination, using a model of human and murine lung cancer cell lines (H125 and 3LL respectively). CIGB-300 presented a lethal dose 50 (LD50) of 119±2.4 μM in H125 cells and 138.3±9.9 μM in 3LL cells. Throughout an Annexin V-FITC assay we could determine that CIGB-300 is a potent apoptosis inductor since the treatment with this drug induced apoptosis at a level comparable with that induced by 10 μM of etoposide. Besides, concomitantly with cell death induction, we could observe the activation of caspase-3 and decreased expression of c-myc and cyclin D1 and D2. The levels of nuclear and cytoplasmic components of the Wnt and NFқB pathways were analyzed by Western blot after treatment with CIGB-300. In the Wnt pathway, a significant decrease in nuclear β-catenin levels could be detected. Related to NFқB pathway, a decrease in the nuclear p65 levels was observed, without affecting cytoplasmic levels of the IқBα inhibitor. Both phenomena could be associated with a reduction in cell survival. Related to metastatic dissemination, we studied in vitro the effect of CIGB-300 on the modulation of the migratory capacity using a wound healing assay. CIGB-300 induced a significant reduction in the migratory potential in a dose dependent way in both 3LL cells (18.86 ± 2.2% vs 32.99 ± 2.7% ¼ and ½ LD50 respectively p