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Antitumor efficacy, pharmacokinetic and biodistribution studies of the anticancer peptide CIGB-552 in mouse models

Item Type:Article
Title:Antitumor efficacy, pharmacokinetic and biodistribution studies of the anticancer peptide CIGB-552 in mouse models
Creators Name:Vallespi, M.G. and Pimentel, G. and Cabrales-Rico, A. and Garza, J. and Oliva, B. and Mendoza, O. and Gomez, Y. and Basaco, T. and Sanchez, I. and Calderon, C. and Rodriguez, J.C. and Markelova, M.R. and Fichtner, I. and Astrada, S. and Bollati-Fogolín, M. and Garay, H.E. and Reyes, O.
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 (131) I-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.
Keywords:COMMD1, Cytotoxic Peptide, Cancer Animal Models, Pharmacokinetic, Cancer Targeted Therapy, Animals, Mice
Source:Journal of Peptide Science
Publisher:Wiley-Blackwell (U.K.)
Page Range:850-859
Date:November 2014
Official Publication:https://doi.org/10.1002/psc.2676
PubMed:View item in PubMed

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