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The Combination of the CIGB-300 Anticancer Peptide and Cisplatin Modulates Proteins Related to Cell Survival, DNA Repair and Metastasis in a Lung Cancer Cell Line Model

[ Vol. 16 , Issue. 4 ]

Author(s):

Arielis Rodríguez-Ulloa*, Yassel Ramos*, Aniel Sánchez-Puente, Yasser Perera, Alexis Musacchio-Lasa , Jorge Fernández-de-Cossio, Gabriel Padrón, Luis J.G. López, Vladimir Besada and Silvio E. Perea   Pages 338 - 349 ( 12 )

Abstract:


Background: CIGB-300 is a pro-apoptotic peptide that abrogates CK2-mediated phosphorylation, and can elicit synergistic interaction in vitro and in vivo when combined with certain anticancer drugs.

Objective: The combination of CIGB-300 with cisplatin is studied through data mining and expressionbased proteomics to reveal the molecular basis of this interaction. Cisplatin resistance-associated proteins, which have also been reported as CK2 substrates, were first identified by bioinformatic analyses.

Methods: Data from these analyses suggested that the cisplatin resistance phenotype could be directly improved by inhibiting CK2 phosphorylation on specific substrates. Furthermore, 157 proteins were differentially modulated on the NCI-H125 lung cancer cell line in response to CIGB-300, cisplatin or both drugs as determined by LC-MS/MS.

Results: The expression of 28 cisplatin resistance-associated proteins was changed when cisplatin was combined with CIGB-300. Overall, the proteins identified are also related to cell survival, cell proliferation and metastasis. Furthermore, the CIGB-300 regulated proteome revealed proteins that were initially involved in the mechanism of action of CIGB-300 and cisplatin as single agents.

Conclusion: This is the first report describing the protein array modulated by combining CIGB-300 and cisplatin that will support the rationale for future clinical settings based on a multi-target cancer therapy.

Keywords:

Comparative proteomic analysis, CIGB-300, cisplatin, apoptosis, casein kinase 2, lung cancer.

Affiliation:

Department of Proteomics, Center for Genetic Engineering and Biotechnology, Havana, Department of Proteomics, Center for Genetic Engineering and Biotechnology, Havana, Department of Proteomics, Center for Genetic Engineering and Biotechnology, Havana, Laboratory of Molecular Oncology, Center for Genetic Engineering and Biotechnology, Havana, Department of Bioinformatics, Center for Genetic Engineering and Biotechnology, Havana, Department of Bioinformatics, Center for Genetic Engineering and Biotechnology, Havana, Department of Proteomics, Center for Genetic Engineering and Biotechnology, Havana, Department of Proteomics, Center for Genetic Engineering and Biotechnology, Havana, Department of Proteomics, Center for Genetic Engineering and Biotechnology, Havana, Laboratory of Molecular Oncology, Center for Genetic Engineering and Biotechnology, Havana

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