Antitumor efficacy,pharmacokinetic and biodistribution studies of the anticancer peptide CIGB‐552 in mouse models |
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Authors: | Maribel G Vallespí Gilmara Pimentel Ania Cabrales‐Rico Julio Garza Brizaida Oliva Osmani Mendoza Yolanda Gomez Tais Basaco Iraida Sánchez Carlos Calderón Juan C Rodriguez Maria Rivera Markelova Iduna Fichtner Soledad Astrada Mariela Bollati‐Fogolín Hilda E Garay Osvaldo Reyes |
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Institution: | 1. Pharmaceutical Department, Center for Genetic Engineering and Biotechnology, , Havana, 10600 Cuba;2. Deparment of Nuclear Medicine, Institute of Oncology and Radiobiology, , Havana, Cuba;3. Synthetic Peptide Group, Chemistry–Physics Department, Center for Genetic Engineering and Biotechnology, , Havana, 10600 Cuba;4. Experimental Pharmacology & Oncology, Berlin‐Buch GmbH, , D‐13122 Berlin, Germany;5. Cell Biology Unit, Institut Pasteur of Montevideo, , Montevideo, 11400 Uruguay |
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Abstract: | Accumulation of the COMMD1 protein as a druggable pharmacology event to target cancer cells has not been evaluated so far in cancer animal models. We have previously demonstrated that a second‐generation peptide, with cell‐penetrating capacity, termed CIGB‐552, was able to induce apoptosis mediated by stabilization of COMMD1. Here, we explore the antitumor effect by subcutaneous administration of CIGB‐552 in a therapeutic schedule. Outstandingly, a significant delay of tumor growth was observed at 0.2 and 0.7 mg/kg (p < 0.01) or 1.4 mg/kg (p < 0.001) after CIGB‐552 administration in both syngeneic murine tumors and patient‐derived xenograft models. Furthermore, we evidenced that 131I‐CIGB‐552 peptide was actually accumulated in the tumors after administration by subcutaneous route. A typical serine‐proteases degradation pattern for CIGB‐552 in BALB/c mice serum was identified. Further, biological characterization of the main metabolites of the peptide CIGB‐552 suggests that the cell‐penetrating capacity plays an important role in the cytotoxic activity. This report is the first in describing the antitumor effect induced by systemic administration of a peptide that targets COMMD1 for stabilization. Moreover, our data reinforce the perspectives of CIGB‐552 for cancer targeted therapy. Copyright © 2014 European Peptide Society and John Wiley & Sons, Ltd. |
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Keywords: | COMMD1 cytotoxic peptide cancer animal models pharmacokinetic cancer targeted therapy |
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