The synthetic peptide CIGB-300 inhibits nuclear factor kB (NF-κB) translocation affecting the survival and chemoresistance of human lung cancer cells

STÉFANO M. CIRIGLIANO; MARÍA INÉS DÍAZ BESSONE; CAROLINA FLUMIAN; DAMIAN E. BERARDI; SILVIO PEREA; ELISA D. BAL DE KIER JOFFE; HERNÁN FARINA; LAURA B. TODARO; ALEJANDRO J. URTREGER

Ciudad Autónoma de Buenos Aires

Simposio; Simposio Internacional: Ganando la Guerra Contra el Cáncer; 2016

Ministerio de Ciencia y Técnica

Introduction. The protein-kinase-2 (CK2) is involved in cell proliferation, survival and apoptosis. CIGB-300 is an antitumor peptide that binds CK2 substrates preventing the enzyme activity.NF-kB activation can reduce chemotherapy efficiency in lung cancer. We have determined that CIGB-300 inhibits NF-κB (p65) nuclear translocation. Also, CIGB-300 alters the ability of lung cancer cells to grow in a three-dimensional spheroid model. Ojbective: To study the treatment efficiency of cisplatin with CIGB-300 and its effect on p65 nuclear levels. To determine proteasome activity after CIGB-300 treatment, given that NF-κB stability is regulated by proteasome-selective proteolysis. To analyze whether CIGB-300 affects spheroid compact structure, that resembles in vivo avascular tumors. Methods: A cisplatin resistant cell line (A549-Rcisp) was developed by chronic administration during six months. Proteasome-selective activity was assessed with Proteasome-Glo Assay (Promega). Biotin-labeled CIGB-300 was used to treat NCI-H125 spheroids at different time points and detected by immunohistochemistry. Discussion and results: Nuclear p65 levels were highly increased after treating human NCI-H125 cells with cisplatin (Western blot). Moreover, when cells were treated with cisplatin plus CIGB-300, NF-κB activation was abolished. Remarkably, in a chemoresistant setting, A549-Rcisp cells showed an increase in CIGB-300 sensitivity compared with the parental cell line (p