A penicillin derivative exerts an anti-metastatic activity in melanoma cells through the downregulation of Integrin αvβ3 and wnt/β-catenin pathway

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Abstact: 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...

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Autores principales: Barrionuevo, Elizabeth, Cayrol, María Florencia, Cremaschi, Graciela A., Cornier, Patricia G., Boggián, Dora B., Delpiccolo, Carina M. L., Mata, Ernesto G., Roguin, Leonor P., Blank, Viviana C.
Formato: Artículo
Lenguaje:Inglés
Publicado: Frontiers Media 2020
Materias:
PENICILINA
TUMORES
MELANOMA
METASTASIS
Acceso en línea:https://repositorio.uca.edu.ar/handle/123456789/10171
Aporte de:
Repositorio Institucional de la Universidad Católica Argentina (UCA) de Universidad Católica Argentina
id I33-R139-123456789-10171
record_format dspace
spelling I33-R139-123456789-101712024-03-21T12:48:02Z A penicillin derivative exerts an anti-metastatic activity in melanoma cells through the downregulation of Integrin αvβ3 and wnt/β-catenin pathway Barrionuevo, Elizabeth Cayrol, María Florencia Cremaschi, Graciela A. Cornier, Patricia G. Boggián, Dora B. Delpiccolo, Carina M. L. Mata, Ernesto G. Roguin, Leonor P. Blank, Viviana C. PENICILINA TUMORES MELANOMA METASTASIS Abstact: 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. 2020-06-10T19:09:49Z 2020-06-10T19:09:49Z 2020 Artículo Barrionuevo, E., et al. A penicillin derivative exerts an anti-metastatic activity in melanoma cells through the downregulation of Integrin αvβ3 and wnt/β-catenin pathway [en línea]. Frontiers in Pharmacology. 2020, 11:127. doi:10.3389/fphar.2020.00127 Disponible en: https://repositorio.uca.edu.ar/handle/123456789/10171 1663-9812 https://repositorio.uca.edu.ar/handle/123456789/10171 10.3389/fphar.2020.00127 32158394 eng Acceso abierto http://creativecommons.org/licenses/by-nc-sa/4.0/ application/pdf Frontiers Media Frontiers in Pharmacology. 2020, 11:127
institution Universidad Católica Argentina
institution_str I-33
repository_str R-139
collection Repositorio Institucional de la Universidad Católica Argentina (UCA)
language Inglés
topic PENICILINA
TUMORES
MELANOMA
METASTASIS
spellingShingle PENICILINA
TUMORES
MELANOMA
METASTASIS
Barrionuevo, Elizabeth
Cayrol, María Florencia
Cremaschi, Graciela A.
Cornier, Patricia G.
Boggián, Dora B.
Delpiccolo, Carina M. L.
Mata, Ernesto G.
Roguin, Leonor P.
Blank, Viviana C.
A penicillin derivative exerts an anti-metastatic activity in melanoma cells through the downregulation of Integrin αvβ3 and wnt/β-catenin pathway
topic_facet PENICILINA
TUMORES
MELANOMA
METASTASIS
description Abstact: 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.
format Artículo
author Barrionuevo, Elizabeth
Cayrol, María Florencia
Cremaschi, Graciela A.
Cornier, Patricia G.
Boggián, Dora B.
Delpiccolo, Carina M. L.
Mata, Ernesto G.
Roguin, Leonor P.
Blank, Viviana C.
author_facet Barrionuevo, Elizabeth
Cayrol, María Florencia
Cremaschi, Graciela A.
Cornier, Patricia G.
Boggián, Dora B.
Delpiccolo, Carina M. L.
Mata, Ernesto G.
Roguin, Leonor P.
Blank, Viviana C.
author_sort Barrionuevo, Elizabeth
title 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_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_sort penicillin derivative exerts an anti-metastatic activity in melanoma cells through the downregulation of integrin αvβ3 and wnt/β-catenin pathway
publisher Frontiers Media
publishDate 2020
url https://repositorio.uca.edu.ar/handle/123456789/10171
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