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Selective Targeting of αvβ5 Integrin in HepG2 Cell Line by RGDechi15D Peptide

Recently, the research community has become increasingly concerned with the receptor αvβ5, a member of the well-known integrin family. Different ongoing studies have evidenced that αvβ5 integrin regulates not only physiological processes but also a wide array of pathological events, suggesting the r...

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Autores principales: Capasso, Domenica, Del Gatto, Annarita, Comegna, Daniela, Russo, Luigi, Fattorusso, Roberto, Saviano, Michele, Di Gaetano, Sonia, Zaccaro, Laura
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7570809/
https://www.ncbi.nlm.nih.gov/pubmed/32961684
http://dx.doi.org/10.3390/molecules25184298
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author Capasso, Domenica
Del Gatto, Annarita
Comegna, Daniela
Russo, Luigi
Fattorusso, Roberto
Saviano, Michele
Di Gaetano, Sonia
Zaccaro, Laura
author_facet Capasso, Domenica
Del Gatto, Annarita
Comegna, Daniela
Russo, Luigi
Fattorusso, Roberto
Saviano, Michele
Di Gaetano, Sonia
Zaccaro, Laura
author_sort Capasso, Domenica
collection PubMed
description Recently, the research community has become increasingly concerned with the receptor αvβ5, a member of the well-known integrin family. Different ongoing studies have evidenced that αvβ5 integrin regulates not only physiological processes but also a wide array of pathological events, suggesting the receptor as a valuable biomarker to specifically target for therapeutic/diagnostic purposes. Remarkably, in some tumors the involvement of the receptor in cell proliferation, tumor dissemination and angiogenesis is well-documented. In this scenario, the availability of a selective αvβ5 antagonist without ‘off-target’ protein effects may improve survival rate in patients with highly aggressive tumors, such as hepatocellular carcinoma. We recently reported a cyclic peptide, RGDechi15D, obtained by structure-activity studies. To our knowledge it represents the first peptide-based molecule reported in the literature able to specifically bind αvβ5 integrin and not cross react with αvβ3. Here we demonstrated the ability of the peptide to diminish both adhesion and invasion of HepG2 cells, an in vitro model system for hepatocellular carcinoma, to reduce the cell proliferation through an apoptotic process, and to interfere with the PI3K pathway. The peptide, also decreases the formation of new vessels in endothelial cells. Taken together these results indicate that the peptide can be considered a promising molecule with properties suited to be assessed in the future for its validation as a selective therapeutic/diagnostic weapon in hepatocarcinoma.
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spelling pubmed-75708092020-10-28 Selective Targeting of αvβ5 Integrin in HepG2 Cell Line by RGDechi15D Peptide Capasso, Domenica Del Gatto, Annarita Comegna, Daniela Russo, Luigi Fattorusso, Roberto Saviano, Michele Di Gaetano, Sonia Zaccaro, Laura Molecules Article Recently, the research community has become increasingly concerned with the receptor αvβ5, a member of the well-known integrin family. Different ongoing studies have evidenced that αvβ5 integrin regulates not only physiological processes but also a wide array of pathological events, suggesting the receptor as a valuable biomarker to specifically target for therapeutic/diagnostic purposes. Remarkably, in some tumors the involvement of the receptor in cell proliferation, tumor dissemination and angiogenesis is well-documented. In this scenario, the availability of a selective αvβ5 antagonist without ‘off-target’ protein effects may improve survival rate in patients with highly aggressive tumors, such as hepatocellular carcinoma. We recently reported a cyclic peptide, RGDechi15D, obtained by structure-activity studies. To our knowledge it represents the first peptide-based molecule reported in the literature able to specifically bind αvβ5 integrin and not cross react with αvβ3. Here we demonstrated the ability of the peptide to diminish both adhesion and invasion of HepG2 cells, an in vitro model system for hepatocellular carcinoma, to reduce the cell proliferation through an apoptotic process, and to interfere with the PI3K pathway. The peptide, also decreases the formation of new vessels in endothelial cells. Taken together these results indicate that the peptide can be considered a promising molecule with properties suited to be assessed in the future for its validation as a selective therapeutic/diagnostic weapon in hepatocarcinoma. MDPI 2020-09-19 /pmc/articles/PMC7570809/ /pubmed/32961684 http://dx.doi.org/10.3390/molecules25184298 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Capasso, Domenica
Del Gatto, Annarita
Comegna, Daniela
Russo, Luigi
Fattorusso, Roberto
Saviano, Michele
Di Gaetano, Sonia
Zaccaro, Laura
Selective Targeting of αvβ5 Integrin in HepG2 Cell Line by RGDechi15D Peptide
title Selective Targeting of αvβ5 Integrin in HepG2 Cell Line by RGDechi15D Peptide
title_full Selective Targeting of αvβ5 Integrin in HepG2 Cell Line by RGDechi15D Peptide
title_fullStr Selective Targeting of αvβ5 Integrin in HepG2 Cell Line by RGDechi15D Peptide
title_full_unstemmed Selective Targeting of αvβ5 Integrin in HepG2 Cell Line by RGDechi15D Peptide
title_short Selective Targeting of αvβ5 Integrin in HepG2 Cell Line by RGDechi15D Peptide
title_sort selective targeting of αvβ5 integrin in hepg2 cell line by rgdechi15d peptide
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7570809/
https://www.ncbi.nlm.nih.gov/pubmed/32961684
http://dx.doi.org/10.3390/molecules25184298
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