Breast cancer remains a leading cause of mortality among women. In metastasis, cascade migration of cancer cells and invasion of extracellular matrix (ECM) represent critical steps. Urokinase-type plasminogen activator (uPA), as well as metalloproteinases MMP-2 and MMP-9, strongly contribute to ECM remodelling, thus becoming associated with tumour migration and invasion. In addition, the high expression of cytoskeletal (CSK) proteins, as fascin, has been correlated with clinically aggressive metastatic tumours, and CSK proteins are thought to affect the migration of cancer cells. Consumption of fruits and vegetables, characterized by high procyanidin content, has been associated to a reduced mortality for breast cancer. Therefore, we investigated the biological effect of grape seed extract (GSE) on the highly metastatic MDA-MB231 breast cancer cell line, focusing on studying GSE ability in inhibiting two main metastatic processes, i.e., cell migration and invasion. After MDA-MB231 breast cancer cells stimulated with GSE migration and invasion were evaluated by means of trans-well assays and uPA as well as MMPs activity was detected by gelatin zymography. Fascin, beta-catenin and nuclear factor-kappa B (NF-kappa B) expression were determined using western blot technique. beta-Catenin localization was observed by confocal microscopy. We observed that high concentrations of GSE inhibited cell proliferation and apoptosis. Conversely, low GSE concentration decreased cell migration and invasion, likely by hampering beta-catenin expression and localization, fascin and NF-kappa B expression, as well as by decreasing the activity of uPA, MMP-2 and MMP-9. These results make GSE a powerful candidate for developing preventive agents against cancer metastasis.

Grape seed extract suppresses MDA-MB231 breast cancer cell migration and invasion / Dinicola, Simona; Alessia, Pasqualato; Cucina, Alessandra; Coluccia, Pier Paolo; Ferranti, Francesca; Canipari, Rita; Catizone, Angiolina; Sara, Proietti; Fabrizio, D'Anselmi; Giulia, Ricci; Alessandro, Palombo; Bizzarri, Mariano. - In: EUROPEAN JOURNAL OF NUTRITION. - ISSN 1436-6207. - STAMPA. - 53:2(2014), pp. 421-431. [10.1007/s00394-013-0542-6]

Grape seed extract suppresses MDA-MB231 breast cancer cell migration and invasion

DINICOLA, SIMONA;CUCINA, Alessandra;COLUCCIA, Pier Paolo;FERRANTI, FRANCESCA;CANIPARI, Rita;CATIZONE, Angiolina;BIZZARRI, Mariano
2014

Abstract

Breast cancer remains a leading cause of mortality among women. In metastasis, cascade migration of cancer cells and invasion of extracellular matrix (ECM) represent critical steps. Urokinase-type plasminogen activator (uPA), as well as metalloproteinases MMP-2 and MMP-9, strongly contribute to ECM remodelling, thus becoming associated with tumour migration and invasion. In addition, the high expression of cytoskeletal (CSK) proteins, as fascin, has been correlated with clinically aggressive metastatic tumours, and CSK proteins are thought to affect the migration of cancer cells. Consumption of fruits and vegetables, characterized by high procyanidin content, has been associated to a reduced mortality for breast cancer. Therefore, we investigated the biological effect of grape seed extract (GSE) on the highly metastatic MDA-MB231 breast cancer cell line, focusing on studying GSE ability in inhibiting two main metastatic processes, i.e., cell migration and invasion. After MDA-MB231 breast cancer cells stimulated with GSE migration and invasion were evaluated by means of trans-well assays and uPA as well as MMPs activity was detected by gelatin zymography. Fascin, beta-catenin and nuclear factor-kappa B (NF-kappa B) expression were determined using western blot technique. beta-Catenin localization was observed by confocal microscopy. We observed that high concentrations of GSE inhibited cell proliferation and apoptosis. Conversely, low GSE concentration decreased cell migration and invasion, likely by hampering beta-catenin expression and localization, fascin and NF-kappa B expression, as well as by decreasing the activity of uPA, MMP-2 and MMP-9. These results make GSE a powerful candidate for developing preventive agents against cancer metastasis.
2014
breast cancer; metalloproteinases; invasion; gse
01 Pubblicazione su rivista::01a Articolo in rivista
Grape seed extract suppresses MDA-MB231 breast cancer cell migration and invasion / Dinicola, Simona; Alessia, Pasqualato; Cucina, Alessandra; Coluccia, Pier Paolo; Ferranti, Francesca; Canipari, Rita; Catizone, Angiolina; Sara, Proietti; Fabrizio, D'Anselmi; Giulia, Ricci; Alessandro, Palombo; Bizzarri, Mariano. - In: EUROPEAN JOURNAL OF NUTRITION. - ISSN 1436-6207. - STAMPA. - 53:2(2014), pp. 421-431. [10.1007/s00394-013-0542-6]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/537413
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