Design and Synthesis of Arf1-Targeting γ-Dipeptides as Potential Agents against Head and Neck Squamous Cell Carcinoma
Background: Head and neck squamous cell carcinoma (HNSCC) is one of the leading causes of cancer-related deaths and calls for new druggable targets. We have previously highlighted the critical role of ADP-ribosylation factor-1 (Arf1) activation in HNSCC. In the present study, we address the question...
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MDPI AG
2020-01-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/9/2/286 |
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| author | Yen Vo-Hoang Sergio Paiva Leilei He Sébastien Estaran Yong Teng |
| author_facet | Yen Vo-Hoang Sergio Paiva Leilei He Sébastien Estaran Yong Teng |
| author_sort | Yen Vo-Hoang |
| collection | DOAJ |
| description | Background: Head and neck squamous cell carcinoma (HNSCC) is one of the leading causes of cancer-related deaths and calls for new druggable targets. We have previously highlighted the critical role of ADP-ribosylation factor-1 (Arf1) activation in HNSCC. In the present study, we address the question whether targeting Arf1 could be proposed as a valuable strategy against HNSCC. Methods: We rationally designed and synthesized constrained ATC-based (4-amino-(methyl)-1,3-thiazole-5-carboxylic acid) γ-dipeptides to block Arf1 activation. We evaluated the effects of these γ-dipeptides in HNSCC cells: The cell viability was determined in 2D and 3D cell cultures after 72 h treatment and Arf1 protein levels and activity were assessed by GGA3 pull-down and Western blotting assays. Results: Targeting Arf1 offers a valuable strategy to counter HNSCC. Our new Arf1-targeting compounds revealed a strong in vitro cytotoxicity against HNSCC cells, through inhibiting Arf1 activation and its downstream pathways. Conclusions: Arf1-targeting γ-dipeptides developed in this study may represent a promising targeted therapeutic to improve managing the HNSCC disease. |
| first_indexed | 2024-03-12T10:22:26Z |
| format | Article |
| id | doaj.art-333ff86a38694d73b36f50d9cc6a05a6 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-12T10:22:26Z |
| publishDate | 2020-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-333ff86a38694d73b36f50d9cc6a05a62023-09-02T10:01:18ZengMDPI AGCells2073-44092020-01-019228610.3390/cells9020286cells9020286Design and Synthesis of Arf1-Targeting γ-Dipeptides as Potential Agents against Head and Neck Squamous Cell CarcinomaYen Vo-Hoang0Sergio Paiva1Leilei He2Sébastien Estaran3Yong Teng4Institut des Biomolécules Max Mousseron, UMR 5247, CNRS-UM-ENSCM, UFR des Sciences Pharmaceutiques et Biologiques, 15 avenue Charles Flahault, 34093 Montpellier CEDEX 5, FranceInstitut des Biomolécules Max Mousseron, UMR 5247, CNRS-UM-ENSCM, UFR des Sciences Pharmaceutiques et Biologiques, 15 avenue Charles Flahault, 34093 Montpellier CEDEX 5, FranceDepartment of Oral Biology and Diagnostic Sciences, Georgia Cancer Center, Augusta University, 1120 15th Street, Augusta, GA 309212, USAInstitut des Biomolécules Max Mousseron, UMR 5247, CNRS-UM-ENSCM, UFR des Sciences Pharmaceutiques et Biologiques, 15 avenue Charles Flahault, 34093 Montpellier CEDEX 5, FranceDepartment of Oral Biology and Diagnostic Sciences, Georgia Cancer Center, Augusta University, 1120 15th Street, Augusta, GA 309212, USABackground: Head and neck squamous cell carcinoma (HNSCC) is one of the leading causes of cancer-related deaths and calls for new druggable targets. We have previously highlighted the critical role of ADP-ribosylation factor-1 (Arf1) activation in HNSCC. In the present study, we address the question whether targeting Arf1 could be proposed as a valuable strategy against HNSCC. Methods: We rationally designed and synthesized constrained ATC-based (4-amino-(methyl)-1,3-thiazole-5-carboxylic acid) γ-dipeptides to block Arf1 activation. We evaluated the effects of these γ-dipeptides in HNSCC cells: The cell viability was determined in 2D and 3D cell cultures after 72 h treatment and Arf1 protein levels and activity were assessed by GGA3 pull-down and Western blotting assays. Results: Targeting Arf1 offers a valuable strategy to counter HNSCC. Our new Arf1-targeting compounds revealed a strong in vitro cytotoxicity against HNSCC cells, through inhibiting Arf1 activation and its downstream pathways. Conclusions: Arf1-targeting γ-dipeptides developed in this study may represent a promising targeted therapeutic to improve managing the HNSCC disease.https://www.mdpi.com/2073-4409/9/2/286hnsccarf1constrained γ-dipeptidesanticancer |
| spellingShingle | Yen Vo-Hoang Sergio Paiva Leilei He Sébastien Estaran Yong Teng Design and Synthesis of Arf1-Targeting γ-Dipeptides as Potential Agents against Head and Neck Squamous Cell Carcinoma Cells hnscc arf1 constrained γ-dipeptides anticancer |
| title | Design and Synthesis of Arf1-Targeting γ-Dipeptides as Potential Agents against Head and Neck Squamous Cell Carcinoma |
| title_full | Design and Synthesis of Arf1-Targeting γ-Dipeptides as Potential Agents against Head and Neck Squamous Cell Carcinoma |
| title_fullStr | Design and Synthesis of Arf1-Targeting γ-Dipeptides as Potential Agents against Head and Neck Squamous Cell Carcinoma |
| title_full_unstemmed | Design and Synthesis of Arf1-Targeting γ-Dipeptides as Potential Agents against Head and Neck Squamous Cell Carcinoma |
| title_short | Design and Synthesis of Arf1-Targeting γ-Dipeptides as Potential Agents against Head and Neck Squamous Cell Carcinoma |
| title_sort | design and synthesis of arf1 targeting γ dipeptides as potential agents against head and neck squamous cell carcinoma |
| topic | hnscc arf1 constrained γ-dipeptides anticancer |
| url | https://www.mdpi.com/2073-4409/9/2/286 |
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