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

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Item Type:	Article
Title:	Antitumor efficacy, pharmacokinetic and biodistribution studies of the anticancer peptide CIGB-552 in mouse models
Creators Name:	Vallespi, M.G., Pimentel, G., Cabrales-Rico, A., Garza, J., Oliva, B., Mendoza, O., Gomez, Y., Basaco, T., Sanchez, I., Calderon, C., Rodriguez, J.C., Markelova, M.R., Fichtner, I., Astrada, S., Bollati-Fogolín, M., 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
ISSN:	1075-2617
Publisher:	Wiley-Blackwell
Volume:	20
Number:	11
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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