IQUIR   05412
INSTITUTO DE QUIMICA ROSARIO
Unidad Ejecutora - UE
artículos
Título:
A penicillin derivative exerts an anti-metastatic activity in melanoma cells through the downregulation of integrin alphavβ3 and Wnt/ β-catenin pathway
Autor/es:
GRACIELA A. CREMASCHI; CARINA M. DELPICCOLO; VIVIANA C. BLANK; FLORENCIA CAYROL; DORA B. BOGGIAN; LEONOR P. ROGUIN; ELIZABETH BARRIONUEVO; PATRICIA G. CORNIER; ERNESTO G. MATA
Revista:
Frontiers in Pharmacology
Editorial:
Frontiers Media SA
Referencias:
Lugar: Lausanne; Año: 2020
ISSN:
1663-9812
Resumen:
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 B16-F10 murine 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 marker vimentin, 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.