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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| Format: | Article |
| Language: | English |
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MDPI AG
2020-09-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/25/18/4298 |
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| author | Domenica Capasso Annarita Del Gatto Daniela Comegna Luigi Russo Roberto Fattorusso Michele Saviano Sonia Di Gaetano Laura Zaccaro |
| author_facet | Domenica Capasso Annarita Del Gatto Daniela Comegna Luigi Russo Roberto Fattorusso Michele Saviano Sonia Di Gaetano Laura Zaccaro |
| author_sort | Domenica Capasso |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-03-10T16:12:31Z |
| format | Article |
| id | doaj.art-5894c390b9be47c8a1da3505ceb39869 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-10T16:12:31Z |
| publishDate | 2020-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-5894c390b9be47c8a1da3505ceb398692023-11-20T14:19:11ZengMDPI AGMolecules1420-30492020-09-012518429810.3390/molecules25184298Selective Targeting of αvβ5 Integrin in HepG2 Cell Line by RGDechi15D PeptideDomenica Capasso0Annarita Del Gatto1Daniela Comegna2Luigi Russo3Roberto Fattorusso4Michele Saviano5Sonia Di Gaetano6Laura Zaccaro7CESTEV, University of Naples “Federico II”, 80145 Naples, ItalyCIRPeB, University of Naples “Federico II”, 80134 Naples, ItalyInstitute of Biostructures and Bioimaging, CNR, 80134 Naples, ItalyDepartment of Environmental, Biological and Pharmaceutical Sciences and Technologies, University of Campania “Luigi Vanvitelli”, 81100 Caserta, ItalyCIRPeB, University of Naples “Federico II”, 80134 Naples, ItalyCIRPeB, University of Naples “Federico II”, 80134 Naples, ItalyCIRPeB, University of Naples “Federico II”, 80134 Naples, ItalyCIRPeB, University of Naples “Federico II”, 80134 Naples, ItalyRecently, 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.https://www.mdpi.com/1420-3049/25/18/4298αvβ5 Integrinpeptide antagonisttumor cell adhesiontumor cell invasionHCCangiogenesis |
| spellingShingle | Domenica Capasso Annarita Del Gatto Daniela Comegna Luigi Russo Roberto Fattorusso Michele Saviano Sonia Di Gaetano Laura Zaccaro Selective Targeting of αvβ5 Integrin in HepG2 Cell Line by RGDechi15D Peptide Molecules αvβ5 Integrin peptide antagonist tumor cell adhesion tumor cell invasion HCC angiogenesis |
| 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 | αvβ5 Integrin peptide antagonist tumor cell adhesion tumor cell invasion HCC angiogenesis |
| url | https://www.mdpi.com/1420-3049/25/18/4298 |
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