INVESTIGADORES
URTREGER Alejandro Jorge
congresos y reuniones científicas
Título:
The synthetic peptide CIGB-300 inhibits nuclear factor kB (NF-kB) affecting the survival and chemoresistance of human lung cancer cells
Autor/es:
STÉFANO M. CIRIGLIANO; MARÍA INÉS DÍAZ BESSONE; CAROLINA FLUMIAN; DAMIAN E. BERARDI; SILVIO PEREA; ELISA BAL DE KIER JOFFÉ; HERNÁN FARINA; LAURA B. TODARO; ALEJANDRO J. URTREGER
Lugar:
New Orleans
Reunión:
Congreso; 107th Annual Meeting of the American Associaton for Cancer Research; 2016
Institución organizadora:
American Associaton for Cancer Research (AACR)
Resumen:
Lung cancer is the leading cause of cancer deaths worldwide and despite significant progress, current therapies are limited in efficacy. The CK2 Ser/Thr kinase has been historically linked with cancer. It is involved in cell proliferation, survival and apoptosis by modulating diverse signaling pathways, including Wnt and NF-κB among the most relevant.CIGB-300 is an antitumor peptide with a novel mechanism of action, capable of binding to CK2 substrates thus preventing the enzyme activity. Previously, we have determined that CIGB-300 induces apoptosis through caspase-3 activation in different lung cancer cell lines. Moreover, CIGB-300 strongly inhibited RelA/NF-κB (p65) nuclear translocation, even in the presence of a phorbol-ester activating stimulus.NF-κB activation is known to reduce chemotherapy efficiency in different malignancies, including lung cancer. Based on this evidence, we hypothesize that supplementing cisplatin with CIGB-300 would improve the treatment efficiency.Indeed, we observed by Western blot that nuclear p65 levels were highly increased after treating human NCI-H125 cells with cisplatin. Moreover, when cells were treated with cisplatin plus CIGB-300, NF-κB activation was completely abolished. Therefore, the CIGB-300 effect on NF-κB signaling pathway prevails over cisplatin.These promising results on NF-κB inhibition led us to evaluate the combined treatment in chemoresistant setting. For this purpose we developed a cisplatin resistant A549 lung cancer cell line (A549-Rcisp) by the chronic administration of cisplatin during six months. A549-Rcisp viability was 40% higher than parental cells, confirming the cisplatin-acquired resistance. Remarkably, cisplatin resistant cells showed a significant increase in CIGB-300 sensitivity as compared to the parental cell line (p