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Pronounced peptide selectivity for melanoma through tryptophan end-tagging
Effects of oligotryptophan end-tagging on the uptake of arginine-rich peptides into melanoma cells was investigated under various conditions and compared to that into non-malignant keratinocytes, fibroblasts, and erythrocytes, also monitoring resulting cell toxicity. In parallel, biophysical studies...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4847013/ https://www.ncbi.nlm.nih.gov/pubmed/27117225 http://dx.doi.org/10.1038/srep24952 |
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author | Duong, Dinh Thuy Singh, Shalini Bagheri, Mojtaba Verma, Navin Kumar Schmidtchen, Artur Malmsten, Martin |
author_facet | Duong, Dinh Thuy Singh, Shalini Bagheri, Mojtaba Verma, Navin Kumar Schmidtchen, Artur Malmsten, Martin |
author_sort | Duong, Dinh Thuy |
collection | PubMed |
description | Effects of oligotryptophan end-tagging on the uptake of arginine-rich peptides into melanoma cells was investigated under various conditions and compared to that into non-malignant keratinocytes, fibroblasts, and erythrocytes, also monitoring resulting cell toxicity. In parallel, biophysical studies on peptide binding to, and destabilization of, model lipid membranes provided mechanistic insight into the origin of the selectivity between melanoma and non-malignant cells. Collectively, the results demonstrate that W-tagging represents a powerful way to increase selective peptide internalization in melanoma cells, resulting in toxicity against these, but not against the non-malignant cells. These effects were shown to be due to increased peptide adsorption to the outer membrane in melanoma cells, caused by the presence of anionic lipids such as phosphatidylserine and ganglioside GM1, and to peptide effects on mitochondria membranes and resulting apoptosis. In addition, the possibility of using W-tagged peptides for targeted uptake of nanoparticles/drug carriers in melanoma was demonstrated, as was the possibility to open up the outer membrane of melanoma cells in order to facilitate uptake of low Mw anticancer drugs, here demonstrated for doxorubicin. |
format | Online Article Text |
id | pubmed-4847013 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-48470132016-05-04 Pronounced peptide selectivity for melanoma through tryptophan end-tagging Duong, Dinh Thuy Singh, Shalini Bagheri, Mojtaba Verma, Navin Kumar Schmidtchen, Artur Malmsten, Martin Sci Rep Article Effects of oligotryptophan end-tagging on the uptake of arginine-rich peptides into melanoma cells was investigated under various conditions and compared to that into non-malignant keratinocytes, fibroblasts, and erythrocytes, also monitoring resulting cell toxicity. In parallel, biophysical studies on peptide binding to, and destabilization of, model lipid membranes provided mechanistic insight into the origin of the selectivity between melanoma and non-malignant cells. Collectively, the results demonstrate that W-tagging represents a powerful way to increase selective peptide internalization in melanoma cells, resulting in toxicity against these, but not against the non-malignant cells. These effects were shown to be due to increased peptide adsorption to the outer membrane in melanoma cells, caused by the presence of anionic lipids such as phosphatidylserine and ganglioside GM1, and to peptide effects on mitochondria membranes and resulting apoptosis. In addition, the possibility of using W-tagged peptides for targeted uptake of nanoparticles/drug carriers in melanoma was demonstrated, as was the possibility to open up the outer membrane of melanoma cells in order to facilitate uptake of low Mw anticancer drugs, here demonstrated for doxorubicin. Nature Publishing Group 2016-04-27 /pmc/articles/PMC4847013/ /pubmed/27117225 http://dx.doi.org/10.1038/srep24952 Text en Copyright © 2016, Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
spellingShingle | Article Duong, Dinh Thuy Singh, Shalini Bagheri, Mojtaba Verma, Navin Kumar Schmidtchen, Artur Malmsten, Martin Pronounced peptide selectivity for melanoma through tryptophan end-tagging |
title | Pronounced peptide selectivity for melanoma through tryptophan end-tagging |
title_full | Pronounced peptide selectivity for melanoma through tryptophan end-tagging |
title_fullStr | Pronounced peptide selectivity for melanoma through tryptophan end-tagging |
title_full_unstemmed | Pronounced peptide selectivity for melanoma through tryptophan end-tagging |
title_short | Pronounced peptide selectivity for melanoma through tryptophan end-tagging |
title_sort | pronounced peptide selectivity for melanoma through tryptophan end-tagging |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4847013/ https://www.ncbi.nlm.nih.gov/pubmed/27117225 http://dx.doi.org/10.1038/srep24952 |
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