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Synergic effect of anticancer peptide CIGB-552 and Cisplatin in lung cancer models

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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.

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Data availability

We declare total transparency with the data generated and presented in the above manuscript.

Code availability

Not applicable.

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Acknowledgements

We would like to thank Freya Milagro Freyre Almeida, Yaima Chacon Quintero, Amalia Vazquez Arteaga, Tania Cardenas Borrego, Rocio Garateix Suarez, Enma Brown Richards, Dagmara Pichardo Diaz and Lizet Aldana Velazco for their advices and collaboration on this experimental work.

Funding

There is no funding source associated with this work.

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Author notes

  1. Yolanda Gomez Rodriguez and Brizaida Oliva Arguelles have contributed equally to this work.

Authors and Affiliations

  1. Pavillon de Recherche Appliquée sur le Cancer (PRAC), Université de Sherbrooke, Sherbrooke, QC, Canada

    Yolanda Gomez Rodriguez

  2. Pharmaceutical Department, Laboratory of Cancer Biology, Center for Genetic Engineering and Biotechnology (CIGB), Cubanacan, P.O. Box 6162, 10600, Havana, Cuba

    Brizaida Oliva Arguelles, Julio Fernandez Masso & Maribel Guerra Vallespi

  3. Leslie Dan Faculty of Pharmacy, University of Toronto, 70 Downswiew avenue, Toronto, ON, M3M1E2, Canada

    Mario Riera-Romo

  4. Department of Bioinformatics, Center for Genetic Engineering and Biotechnology (CIGB), Havana, Cuba

    Jorge Fernandez-De-Cossio

  5. Peptide Synthesis Division, Center for Genetic Engineering and Biotechnology (CIGB), Havana, Cuba

    Hilda Elisa Garay

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  1. Yolanda Gomez Rodriguez
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  2. Brizaida Oliva Arguelles
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Contributions

YGR, BOA, JF-C, HEG, JFM, MGV—Substantial contributions to the conception or design of the work; or the acquisition, analysis, or interpretation of data for the work. BOA, MR-R, YGR, MGV—Drafting the work or revising it critically for important intellectual content, final approval of the version to be published. YGR, BOA, MGV—Agreement to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Corresponding author

Correspondence to Brizaida Oliva Arguelles.

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Authors do not declare any conflict of interests associated to this work.

Ethical approval

All animal experiments were performed in accordance with the recommendations for the proper use and care of laboratory animals at the Center for Genetic Engineering and Biotechnology (Havana, Cuba) and were previously approved by this ethical committee. This animal study complies with all the international requirements and is according the National Institutes of Health guide for care and use of laboratory animals.

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Gomez Rodriguez, Y., Oliva Arguelles, B., Riera-Romo, M. et al. Synergic effect of anticancer peptide CIGB-552 and Cisplatin in lung cancer models. Mol Biol Rep 49, 3197–3212 (2022). https://doi.org/10.1007/s11033-022-07152-3

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