Cell Penetrating Capacity and Internalization Mechanisms Used by the Synthetic Peptide CIGB-552 and Its Relationship with Tumor Cell Line Sensitivity
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 throu...
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| Format: | Article |
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MDPI AG
2018-03-01
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| Series: | Molecules |
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| Online Access: | http://www.mdpi.com/1420-3049/23/4/801 |
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| author | Soledad Astrada Julio Raúl Fernández Massó Maribel G. Vallespí Mariela Bollati-Fogolín |
| author_facet | Soledad Astrada Julio Raúl Fernández Massó Maribel G. Vallespí Mariela Bollati-Fogolín |
| author_sort | Soledad Astrada |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-22T01:07:37Z |
| format | Article |
| id | doaj.art-76c1535cac604d60afcbf9000b8faab0 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-12-22T01:07:37Z |
| publishDate | 2018-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-76c1535cac604d60afcbf9000b8faab02022-12-21T18:44:03ZengMDPI AGMolecules1420-30492018-03-0123480110.3390/molecules23040801molecules23040801Cell Penetrating Capacity and Internalization Mechanisms Used by the Synthetic Peptide CIGB-552 and Its Relationship with Tumor Cell Line SensitivitySoledad Astrada0Julio Raúl Fernández Massó1Maribel G. Vallespí2Mariela Bollati-Fogolín3Cell Biology Unit, Institut Pasteur de Montevideo, Mataojo 2020, 11400 Montevideo, UruguayDepartment of Genomic, Center for Genetic Engineering and Biotechnology, Cubanacan, P.O. Box 6162, Havana 10600, CubaPharmaceutical Department, Center for Genetic Engineering and Biotechnology, Cubanacan, P.O. Box 6162, Havana 10600, CubaCell Biology Unit, Institut Pasteur de Montevideo, Mataojo 2020, 11400 Montevideo, UruguayCIGB-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.http://www.mdpi.com/1420-3049/23/4/801cell penetrating peptideendocytosistransduction |
| spellingShingle | Soledad Astrada Julio Raúl Fernández Massó Maribel G. Vallespí Mariela Bollati-Fogolín Cell Penetrating Capacity and Internalization Mechanisms Used by the Synthetic Peptide CIGB-552 and Its Relationship with Tumor Cell Line Sensitivity Molecules cell penetrating peptide endocytosis transduction |
| title | Cell Penetrating Capacity and Internalization Mechanisms Used by the Synthetic Peptide CIGB-552 and Its Relationship with Tumor Cell Line Sensitivity |
| title_full | Cell Penetrating Capacity and Internalization Mechanisms Used by the Synthetic Peptide CIGB-552 and Its Relationship with Tumor Cell Line Sensitivity |
| title_fullStr | Cell Penetrating Capacity and Internalization Mechanisms Used by the Synthetic Peptide CIGB-552 and Its Relationship with Tumor Cell Line Sensitivity |
| title_full_unstemmed | Cell Penetrating Capacity and Internalization Mechanisms Used by the Synthetic Peptide CIGB-552 and Its Relationship with Tumor Cell Line Sensitivity |
| title_short | Cell Penetrating Capacity and Internalization Mechanisms Used by the Synthetic Peptide CIGB-552 and Its Relationship with Tumor Cell Line Sensitivity |
| title_sort | cell penetrating capacity and internalization mechanisms used by the synthetic peptide cigb 552 and its relationship with tumor cell line sensitivity |
| topic | cell penetrating peptide endocytosis transduction |
| url | http://www.mdpi.com/1420-3049/23/4/801 |
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