A Penicillin Derivative Exerts an Anti-Metastatic Activity in Melanoma Cells Through the Downregulation of Integrin αvβ3 and Wnt/β-Catenin Pathway
The synthetic triazolylpeptidyl penicillin derivative, named TAP7f, has been previously characterized as an effective antitumor agent in vitro and in vivo against B16-F0 melanoma cells. In this study, we investigated the anti-metastatic potential of this compound on highly metastatic murine B16-F10...
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Frontiers Media S.A.
2020-02-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fphar.2020.00127/full |
| _version_ | 1818207119338373120 |
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| author | Elizabeth Barrionuevo Florencia Cayrol Graciela A. Cremaschi Patricia G. Cornier Dora B. Boggián Carina M. L. Delpiccolo Ernesto G. Mata Leonor P. Roguin Viviana C. Blank |
| author_facet | Elizabeth Barrionuevo Florencia Cayrol Graciela A. Cremaschi Patricia G. Cornier Dora B. Boggián Carina M. L. Delpiccolo Ernesto G. Mata Leonor P. Roguin Viviana C. Blank |
| author_sort | Elizabeth Barrionuevo |
| collection | DOAJ |
| description | The synthetic triazolylpeptidyl penicillin derivative, named TAP7f, has been previously characterized as an effective antitumor agent in vitro and in vivo against B16-F0 melanoma cells. In this study, we investigated the anti-metastatic potential of this compound on highly metastatic murine B16-F10 and human A375 melanoma cells. We found that TAP7f inhibited cell adhesion, migration and invasion in a dose-dependent manner. Additionally, we demonstrated that TAP7f downregulated integrin αvβ3 expression and Wnt/β-catenin pathway, a signaling cascade commonly related to tumor invasion and metastasis. Thus, TAP7f reduced both the enzymatic activity and the expression levels of matrix-metalloproteinases-2 and -9 in a time dependent manner. Moreover, TAP7f inhibited the expression of the transcription factor Snail and the mesenchymal markers vimentin, and N-cadherin, and up-regulated the expression of the epithelial marker E-cadherin, suggesting that the penicillin derivative affects epithelial–mesenchymal transition. Results obtained in vitro were supported by those obtained in a B16-F10-bearing mice metastatic model, that showed a significant TAP7f inhibition of lung metastasis. These findings suggest the potential of TAP7f as a chemotherapeutic agent for the treatment of metastatic melanoma. |
| first_indexed | 2024-12-12T04:23:51Z |
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| id | doaj.art-aa779f640d1a4392bc3ab33af106ce02 |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-12-12T04:23:51Z |
| publishDate | 2020-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj.art-aa779f640d1a4392bc3ab33af106ce022022-12-22T00:38:15ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122020-02-011110.3389/fphar.2020.00127503824A Penicillin Derivative Exerts an Anti-Metastatic Activity in Melanoma Cells Through the Downregulation of Integrin αvβ3 and Wnt/β-Catenin PathwayElizabeth Barrionuevo0Florencia Cayrol1Graciela A. Cremaschi2Patricia G. Cornier3Dora B. Boggián4Carina M. L. Delpiccolo5Ernesto G. Mata6Leonor P. Roguin7Viviana C. Blank8Laboratorio de Oncología y Transducción de Señales, Instituto de Química y Fisicoquímica Biológicas (IQUIFIB), Departamento de Química Biológica, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, CONICET, Buenos Aires, ArgentinaLaboratorio de Neuroinmunomodulación y Oncología Molecular, Instituto de Investigaciones Biomédicas, Facultad de Ciencias Médicas, Pontificia Universidad Católica Argentina (UCA), CONICET, Buenos Aires, ArgentinaLaboratorio de Neuroinmunomodulación y Oncología Molecular, Instituto de Investigaciones Biomédicas, Facultad de Ciencias Médicas, Pontificia Universidad Católica Argentina (UCA), CONICET, Buenos Aires, ArgentinaLaboratorio de Química Orgánica, Instituto de Química Rosario (CONICET-UNR), Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario, Rosario, ArgentinaLaboratorio de Química Orgánica, Instituto de Química Rosario (CONICET-UNR), Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario, Rosario, ArgentinaLaboratorio de Química Orgánica, Instituto de Química Rosario (CONICET-UNR), Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario, Rosario, ArgentinaLaboratorio de Química Orgánica, Instituto de Química Rosario (CONICET-UNR), Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario, Rosario, ArgentinaLaboratorio de Oncología y Transducción de Señales, Instituto de Química y Fisicoquímica Biológicas (IQUIFIB), Departamento de Química Biológica, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, CONICET, Buenos Aires, ArgentinaLaboratorio de Oncología y Transducción de Señales, Instituto de Química y Fisicoquímica Biológicas (IQUIFIB), Departamento de Química Biológica, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, CONICET, Buenos Aires, ArgentinaThe synthetic triazolylpeptidyl penicillin derivative, named TAP7f, has been previously characterized as an effective antitumor agent in vitro and in vivo against B16-F0 melanoma cells. In this study, we investigated the anti-metastatic potential of this compound on highly metastatic murine B16-F10 and human A375 melanoma cells. We found that TAP7f inhibited cell adhesion, migration and invasion in a dose-dependent manner. Additionally, we demonstrated that TAP7f downregulated integrin αvβ3 expression and Wnt/β-catenin pathway, a signaling cascade commonly related to tumor invasion and metastasis. Thus, TAP7f reduced both the enzymatic activity and the expression levels of matrix-metalloproteinases-2 and -9 in a time dependent manner. Moreover, TAP7f inhibited the expression of the transcription factor Snail and the mesenchymal markers vimentin, and N-cadherin, and up-regulated the expression of the epithelial marker E-cadherin, suggesting that the penicillin derivative affects epithelial–mesenchymal transition. Results obtained in vitro were supported by those obtained in a B16-F10-bearing mice metastatic model, that showed a significant TAP7f inhibition of lung metastasis. These findings suggest the potential of TAP7f as a chemotherapeutic agent for the treatment of metastatic melanoma.https://www.frontiersin.org/article/10.3389/fphar.2020.00127/fulltriazolylpeptidyl penicillinanti-metastatic effectmurine melanomaβ-cateninmetalloproteinases-2 and -9integrin αvβ3 |
| spellingShingle | Elizabeth Barrionuevo Florencia Cayrol Graciela A. Cremaschi Patricia G. Cornier Dora B. Boggián Carina M. L. Delpiccolo Ernesto G. Mata Leonor P. Roguin Viviana C. Blank A Penicillin Derivative Exerts an Anti-Metastatic Activity in Melanoma Cells Through the Downregulation of Integrin αvβ3 and Wnt/β-Catenin Pathway Frontiers in Pharmacology triazolylpeptidyl penicillin anti-metastatic effect murine melanoma β-catenin metalloproteinases-2 and -9 integrin αvβ3 |
| title | A Penicillin Derivative Exerts an Anti-Metastatic Activity in Melanoma Cells Through the Downregulation of Integrin αvβ3 and Wnt/β-Catenin Pathway |
| title_full | A Penicillin Derivative Exerts an Anti-Metastatic Activity in Melanoma Cells Through the Downregulation of Integrin αvβ3 and Wnt/β-Catenin Pathway |
| title_fullStr | A Penicillin Derivative Exerts an Anti-Metastatic Activity in Melanoma Cells Through the Downregulation of Integrin αvβ3 and Wnt/β-Catenin Pathway |
| title_full_unstemmed | A Penicillin Derivative Exerts an Anti-Metastatic Activity in Melanoma Cells Through the Downregulation of Integrin αvβ3 and Wnt/β-Catenin Pathway |
| title_short | A Penicillin Derivative Exerts an Anti-Metastatic Activity in Melanoma Cells Through the Downregulation of Integrin αvβ3 and Wnt/β-Catenin Pathway |
| title_sort | penicillin derivative exerts an anti metastatic activity in melanoma cells through the downregulation of integrin αvβ3 and wnt β catenin pathway |
| topic | triazolylpeptidyl penicillin anti-metastatic effect murine melanoma β-catenin metalloproteinases-2 and -9 integrin αvβ3 |
| url | https://www.frontiersin.org/article/10.3389/fphar.2020.00127/full |
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