Yolanda Gomez Rodriguez1, Brizaida Oliva Arguelles2, Mario Riera-Romo3, Jorge Fernandez-De-Cossio4, Hilda Elisa Garay5, Julio Fernandez Masso6, Maribel Guerra Vallespi6. 1. Pavillon de Recherche Appliquée sur le Cancer (PRAC), Université de Sherbrooke, Sherbrooke, QC, Canada. 2. Pharmaceutical Department, Laboratory of Cancer Biology, Center for Genetic Engineering and Biotechnology (CIGB), Cubanacan, P.O. Box 6162, 10600, Havana, Cuba. brizaida.oliva@gmail.com. 3. Leslie Dan Faculty of Pharmacy, University of Toronto, 70 Downswiew avenue, Toronto, ON, M3M1E2, Canada. 4. Department of Bioinformatics, Center for Genetic Engineering and Biotechnology (CIGB), Havana, Cuba. 5. Peptide Synthesis Division, Center for Genetic Engineering and Biotechnology (CIGB), Havana, Cuba. 6. Pharmaceutical Department, Laboratory of Cancer Biology, Center for Genetic Engineering and Biotechnology (CIGB), Cubanacan, P.O. Box 6162, 10600, Havana, Cuba.
Abstract
BACKGROUND: The antitumor peptide CIGB-552 is a new targeted anticancer therapy which molecular mechanism is associated with the inhibition of the transcription factor NF-kB, mediated by COMMD1 protein stabilization. In this study, we examined the antiproliferative capacity of CIGB-552 in combination with chemotherapeutic agents in lung cancer models. METHODS AND RESULTS: We combined of CIGB-552 and the antineoplastic agent Cisplatin (CDDP) in concomitant and pre-treatment scenary in a dose matrix approach. This study was performed in the non-small cell lung cancer cell lines NCI-H460, A549 and in a mouse model of TC-1 lung cancer. Our results demonstrate a clear synergic effect between 37.5 μM of CIGB-552 and 5 μM of CDDP under concomitant scheme, on proliferation inhibition, cell cycle arrest, apoptosis induction and oxidative stress response. The effect of CIGB-552 (1 mg/kg) and CDDP (0.4 mg/kg) administrated as a combined therapy was demonstrated in vivo in a TC-1 mouse model where the combination achieved an effective antitumor response, without any deterioration signs or side effects. CONCLUSIONS: These findings demonstrate the efficacy of the concomitant combination of both drugs in preclinical studies and support the use of this therapy in clinical trials. This study is the first evidence of synergistic effect of the combination of the antitumoral peptide CIGB-552 and CDDP.
BACKGROUND: The antitumor peptide CIGB-552 is a new targeted anticancer therapy which molecular mechanism is associated with the inhibition of the transcription factor NF-kB, mediated by COMMD1 protein stabilization. In this study, we examined the antiproliferative capacity of CIGB-552 in combination with chemotherapeutic agents in lung cancer models. METHODS AND RESULTS: We combined of CIGB-552 and the antineoplastic agent Cisplatin (CDDP) in concomitant and pre-treatment scenary in a dose matrix approach. This study was performed in the non-small cell lung cancer cell lines NCI-H460, A549 and in a mouse model of TC-1 lung cancer. Our results demonstrate a clear synergic effect between 37.5 μM of CIGB-552 and 5 μM of CDDP under concomitant scheme, on proliferation inhibition, cell cycle arrest, apoptosis induction and oxidative stress response. The effect of CIGB-552 (1 mg/kg) and CDDP (0.4 mg/kg) administrated as a combined therapy was demonstrated in vivo in a TC-1 mouse model where the combination achieved an effective antitumor response, without any deterioration signs or side effects. CONCLUSIONS: These findings demonstrate the efficacy of the concomitant combination of both drugs in preclinical studies and support the use of this therapy in clinical trials. This study is the first evidence of synergistic effect of the combination of the antitumoral peptide CIGB-552 and CDDP.
Authors: Freddie Bray; Jacques Ferlay; Isabelle Soerjomataram; Rebecca L Siegel; Lindsey A Torre; Ahmedin Jemal Journal: CA Cancer J Clin Date: 2018-09-12 Impact factor: 508.702