A Penicillin Derivative Exerts an Anti-Metastatic Activity in Melanoma Cells Through the Downregulation of Integrin αvβ3 and Wnt/β-Catenin Pathway

Copyright © 2020 Barrionuevo, Cayrol, Cremaschi, Cornier, Boggián, Delpiccolo, Mata, Roguin and Blank..

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.

Media Type:

Electronic Article

Year of Publication:

2020

Publication:

2020

Contained In:

To Main Record - volume:11

Contained In:

Frontiers in pharmacology - 11(2020) vom: 30., Seite 127

Language:

English

Contributors:

Barrionuevo, Elizabeth [Author]
Cayrol, Florencia [Author]
Cremaschi, Graciela A [Author]
Cornier, Patricia G [Author]
Boggián, Dora B [Author]
Delpiccolo, Carina M L [Author]
Mata, Ernesto G [Author]
Roguin, Leonor P [Author]
Blank, Viviana C [Author]

Links:

Volltext

Keywords:

β-catenin
Anti-metastatic effect
Integrin αvβ3
Journal Article
Metalloproteinases-2 and -9
Murine melanoma
Triazolylpeptidyl penicillin

Notes:

Date Revised 28.09.2020

published: Electronic-eCollection

Citation Status PubMed-not-MEDLINE

doi:

10.3389/fphar.2020.00127

funding:

Supporting institution / Project title:

PPN (Catalogue-ID):

NLM307546128