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Molecules 2018, 23(4), 801; https://doi.org/10.3390/molecules23040801

Cell Penetrating Capacity and Internalization Mechanisms Used by the Synthetic Peptide CIGB-552 and Its Relationship with Tumor Cell Line Sensitivity

1
Cell Biology Unit, Institut Pasteur de Montevideo, Mataojo 2020, 11400 Montevideo, Uruguay
2
Department of Genomic, Center for Genetic Engineering and Biotechnology, Cubanacan, P.O. Box 6162, Havana 10600, Cuba
3
Pharmaceutical Department, Center for Genetic Engineering and Biotechnology, Cubanacan, P.O. Box 6162, Havana 10600, Cuba
*
Author to whom correspondence should be addressed.
Received: 17 February 2018 / Revised: 26 March 2018 / Accepted: 27 March 2018 / Published: 30 March 2018
(This article belongs to the Special Issue Peptide Therapeutics)
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Abstract

CIGB-552 is a twenty-amino-acid novel synthetic peptide that has proven to be effective in reducing tumor size and increasing lifespan in tumor-bearing mice. Such capability is conferred by its cell-penetrating peptide character, which allows it to enter cells and elicit a pro-apoptotic effect through its major mediator, COMMD1 protein. Cell-penetrating peptides are able to use different internalization mechanisms, such as endocytosis or direct transduction through the plasma membrane. Although CIGB-552 cytotoxicity has been evaluated in several non-tumor- and tumor-derived cell lines, no data regarding the relationship between cell line sensitivity, cell penetrating capacity, the internalization mechanisms involved, COMMD1 expression levels, or its subcellular localization has yet been produced. Here, we present the results obtained from a comparative analysis of CIGB-552 sensitivity, internalization capacity and the mechanisms involved in three human tumor-derived cell lines from different origins: mammary gland, colon and lung (MCF-7, HT-29 and H460, respectively). Furthermore, cell surface markers relevant for internalization processes such as phosphatidylserine, as well as CIGB-552 target COMMD1 expression/localization, were also evaluated. We found that both endocytosis and transduction are involved in CIGB-552 internalization in the three cell lines evaluated. However, CIGB-552 incorporation efficiency and contribution of each mechanism is cell-line dependent. Finally, sensitivity was directly correlated with high internalization capacity in those cell lines where endocytosis had a major contribution on CIGB-552 internalization. View Full-Text
Keywords: cell penetrating peptide; endocytosis; transduction cell penetrating peptide; endocytosis; transduction
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).
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Astrada, S.; Fernández Massó, J.R.; Vallespí, M.G.; Bollati-Fogolín, M. Cell Penetrating Capacity and Internalization Mechanisms Used by the Synthetic Peptide CIGB-552 and Its Relationship with Tumor Cell Line Sensitivity. Molecules 2018, 23, 801.

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