Preclinical efficacy of CIGB-300, an anti-CK2 peptide, on breast cancer metastasic colonization
Autor: | Johanna E. Sidabra, Silvio E. Perea, Hernan G. Farina, Carla S. Capobianco, Maria F. Gottardo, Yasser Perera, Daniel F. Alonso, Juan Garona |
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Jazyk: | angličtina |
Rok vydání: | 2020 |
Předmět: |
0301 basic medicine
Cell cycle checkpoint Lung Neoplasms lcsh:Medicine Antineoplastic Agents Apoptosis Breast Neoplasms Peptides Cyclic Article Metastasis 03 medical and health sciences Breast cancer 0302 clinical medicine Cell Line Tumor medicine Adjuvant therapy Animals Humans Neoplasm Invasiveness Clonogenic assay Cell adhesion Casein Kinase II lcsh:Science Protein Kinase Inhibitors Cell Proliferation Mice Inbred BALB C Multidisciplinary Lung Kinase business.industry lcsh:R medicine.disease 030104 developmental biology medicine.anatomical_structure Mechanism of action 030220 oncology & carcinogenesis Cancer research MCF-7 Cells Female lcsh:Q medicine.symptom business |
Zdroj: | Scientific Reports, Vol 10, Iss 1, Pp 1-11 (2020) Scientific Reports |
ISSN: | 2045-2322 |
DOI: | 10.1038/s41598-020-71854-6 |
Popis: | CK2 is a serine/threonine kinase that is overexpressed in breast cancer and its inhibition is associated to reduced tumor growth and disease progression. CIGB-300 is an antitumor peptide with a novel mechanism of action, since it binds to protein kinase CK2 catalytic subunit alpha and to CK2 substrates thus preventing the enzyme activity. Our aim was to evaluate the potential therapeutic benefits of CIGB-300 on breast cancer disease using experimental models with translational relevance. We demonstrated that CIGB-300 reduces breast cancer cell growth in MDA-MB-231, MCF-7 and F3II cells, exerting a pro-apoptotic action and cell cycle arrest. We also found that CIGB-300 decreased cell adhesion, migration and clonogenic capacity of malignant cells. Effect on experimental breast cancer lung metastasis was evaluated after surgical removal of primary F3II tumors or after tail vein injection of tumor cells, also we evaluated CIGB-300 effect on spontaneous lung metastasis in an orthotopic model. Systemic CIGB-300 treatment inhibited breast cancer colonization of the lung, reducing the size and number of metastatic lesions. The present preclinical study establishes for the first time the efficacy of CIGB-300 on breast cancer. These encouraging results suggest that CIGB-300 could be used for the management of breast cancer as an adjuvant therapy after surgery, limiting tumor metastatic spread and thus protecting the patient from distant recurrence. |
Databáze: | OpenAIRE |
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