In:
Journal of Peptide Science, Wiley, Vol. 20, No. 11 ( 2014-11), p. 850-859
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. Copyright © 2014 European Peptide Society and John Wiley & Sons, Ltd.
Type of Medium:
Online Resource
ISSN:
1075-2617
,
1099-1387
Language:
English
Publisher:
Wiley
Publication Date:
2014
detail.hit.zdb_id:
1491819-5
SSG:
12
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