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Title: Synergic effects of anticancer peptide CIGB-552 and Cisplatin in lung cancer models
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  • Yolanda Gomez Rodriguez,
  • Brizaida Oliva Arguelles,
  • Mario Riera-Romo,
  • Jorge Fernandez de Cossio Dorta Duque ,
  • Freya Freyre Almeida,
  • Yaima Chacon Quintero,
  • Amalia Vazquez Arteaga,
  • Tania Cardenas Borrego,
  • Rocio Garateix Suarez,
  • Enma Brown Richards,
  • Dagmara Pichardo Diaz,
  • Lizet Aldana Velazco,
  • Hilda Elisa Garay,
  • Julio Raúl Fernández Massó,
  • Maribel Guerra Vallespi
Yolanda Gomez Rodriguez
Université de Sherbrooke
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Brizaida Oliva Arguelles
Center for Genetic Engineering and Biotechnology

Corresponding Author:[email protected]

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Mario Riera-Romo
Leiden Universitair Medisch Centrum
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Jorge Fernandez de Cossio Dorta Duque
Center for Genetic Engineering and Biotechnology
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Freya Freyre Almeida
Center for Genetic Engineering and Biotechnology
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Yaima Chacon Quintero
Center for Genetic Engineering and Biotechnology
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Amalia Vazquez Arteaga
Center for Genetic Engineering and Biotechnology
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Tania Cardenas Borrego
Center for Genetic Engineering and Biotechnology
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Rocio Garateix Suarez
Center for Genetic Engineering and Biotechnology
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Enma Brown Richards
Center for Genetic Engineering and Biotechnology
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Dagmara Pichardo Diaz
Center for Genetic Engineering and Biotechnology
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Lizet Aldana Velazco
Center for Genetic Engineering and Biotechnology
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Hilda Elisa Garay
Center for Genetic Engineering and Biotechnology
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Julio Raúl Fernández Massó
Centro de Ingenieria Genetica y Biotecnologia
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Maribel Guerra Vallespi
Center for Genetic Engineering and Biotechnology
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Abstract

Non-small cell lung cancer constitutes one the most frequent and lethal forms of the disease. 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. However, its pharmacological potential in combination with chemotherapy is unknown. In this study, we examined the antiproliferative capacity of CIGB-552 in combination with chemotherapeutic agents in the non-small cell lung cancer cell line NCI-H460 and we confirmed drug interactions in vivo, in a mouse model of TC-1 lung cancer. We focus our research in the combination of CIGB-552 and the antineoplastic agent Cisplatin (CDDP) in a concomitant treatment. 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 the TC-1 murine model where the combination achieved an effective antitumor response, without any deterioration signs or side effects. 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.