URTREGER Alejandro Jorge
congresos y reuniones científicas
Effect of the CIGB-300 synthetic peptide in the modulation of signaling pathways involved with malignant progression of human and murine lung tumors
STÉFANO M. CIRIGLIANO; MARIA I. DIAZ BESSONE; CAROLINA FLUMIAN; DAMIAN E. BERARDI; ELISA D. BAL DE KIER JOFFÉ; HERNÁN FARINA; LAURA B. TODARO; ALEJANDRO J. URTREGER
Congreso; Advances in Molecular Oncology: Translating Molecular Biology into Cancer Treatment; 2013
Sao Paulo School of Advances Sciences
CK2 is a serine/threonine kinase involved in cell growth, survival and apoptosis. CIGB-300 is a synthetic peptide capable of binding to CK2 substrates thus preventing the enzyme activity. We have studied the effect of CIGB-300 on several signaling pathways involved in tumor progression, cell cycle, apoptosis and migration, 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 uM in H125 cells and 138.3±9.9 uM in 3LL cells. Throughout an Annexin V-FITC assay we could determine that CIGB-300 is a potent apoptosis inductor. 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 NFkB pathways were analyzed by Western blot after treatment with CIGB-300. In the Wnt pathway, a significant decrease in nuclear b-catenin levels could be detected. Related to NFkB pathway, a decrease in the nuclear p65 levels was observed. 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 and H125. Our results indicate that the treatment with CIGB-300 induces apoptosis and negatively modulates several signaling pathways involved in malignant progression. This drug may become a new strategy for treatment of lung cancer.