CIGB-300 Anticancer Peptide Differentially Interacts with CK2 Subunits and Regulates Specific Signaling Mediators in a Highly Sensitive Large Cell Lung Carcinoma Cell Model.

Autor: Pérez GV; Molecular Oncology Group, Department of Pharmaceuticals, Biomedical Research Division, Center for Genetic Engineering & Biotechnology (CIGB), Havana 10600, Cuba., Rosales M; Molecular Oncology Group, Department of Pharmaceuticals, Biomedical Research Division, Center for Genetic Engineering & Biotechnology (CIGB), Havana 10600, Cuba.; Department of Animal and Human Biology, Faculty of Biology, University of Havana (UH), Havana 10400, Cuba., Ramón AC; Molecular Oncology Group, Department of Pharmaceuticals, Biomedical Research Division, Center for Genetic Engineering & Biotechnology (CIGB), Havana 10600, Cuba., Rodríguez-Ulloa A; Mass Spectrometry Laboratory, Proteomics Group, Department of System Biology, Biomedical Research Division, CIGB, Havana 10600, Cuba., Besada V; Mass Spectrometry Laboratory, Proteomics Group, Department of System Biology, Biomedical Research Division, CIGB, Havana 10600, Cuba., González LJ; Mass Spectrometry Laboratory, Proteomics Group, Department of System Biology, Biomedical Research Division, CIGB, Havana 10600, Cuba., Aguilar D; Molecular Oncology Group, Department of Pharmaceuticals, Biomedical Research Division, Center for Genetic Engineering & Biotechnology (CIGB), Havana 10600, Cuba., Vázquez-Blomquist D; Pharmacogenomic Group, Department of System Biology, Biomedical Research Division, CIGB, Havana 10600, Cuba., Falcón V; Microscopy Laboratory, Department of System Biology, Biomedical Research Division, CIGB, Havana 10600, Cuba., Caballero E; Molecular Oncology Group, Department of Pharmaceuticals, Biomedical Research Division, Center for Genetic Engineering & Biotechnology (CIGB), Havana 10600, Cuba., Carvalho PC; Laboratory for Structural and Computational Proteomics, Carlos Chagas Institute, Fiocruz-Paraná, R. Professor Algacyr Munhoz Mader 3775, Curitiba 81310-020, PR, Brazil., Caldeira RS; Mass Spectrometry Facility, Carlos Chagas Institute, Fiocruz-Paraná, R. Professor Algacyr Munhoz Mader 3775, Curitiba 81310-020, PR, Brazil., Yang K; China-Cuba Biotechnology Joint Innovation Center (CCBJIC), Yongzhou Zhong Gu Biotechnology, Yongzhou 425000, China., Perera Y; Molecular Oncology Group, Department of Pharmaceuticals, Biomedical Research Division, Center for Genetic Engineering & Biotechnology (CIGB), Havana 10600, Cuba.; China-Cuba Biotechnology Joint Innovation Center (CCBJIC), Yongzhou Zhong Gu Biotechnology, Yongzhou 425000, China., Perea SE; Molecular Oncology Group, Department of Pharmaceuticals, Biomedical Research Division, Center for Genetic Engineering & Biotechnology (CIGB), Havana 10600, Cuba.
Jazyk: angličtina
Zdroj: Biomedicines [Biomedicines] 2022 Dec 25; Vol. 11 (1). Date of Electronic Publication: 2022 Dec 25.
DOI: 10.3390/biomedicines11010043
Abstrakt: Large cell lung carcinoma (LCLC) is one form of NSCLC that spreads more aggressively than some other forms, and it represents an unmet medical need. Here, we investigated for the first time the effect of the anti-CK2 CIGB-300 peptide in NCI-H460 cells as an LCLC model. NCI-H460 cells were highly sensitive toward CIGB-300 cytotoxicity, reaching a peak of apoptosis at 6 h. Moreover, CIGB-300 slightly impaired the cell cycle of NCI-H460 cells. The CIGB-300 interactomics profile revealed in more than 300 proteins that many of them participated in biological processes relevant in cancer. Interrogation of the CK2 subunits targeting by CIGB-300 indicated the higher binding of the peptide to the CK2α' catalytic subunit by in vivo pull-down assays plus immunoblotting analysis and confocal microscopy. The down-regulation of both phosphorylation and protein levels of the ribonuclear protein S6 (RPS6) was observed 48 h post treatment. Altogether, we have found that NCI-H460 cells are the most CIGB-300-sensitive solid tumor cell line described so far, and also, the findings we provide here uncover novel features linked to CK2 targeting by the CIGB-300 anticancer peptide.
Databáze: MEDLINE
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