title: Grape seed extract suppresses MDA-MB231 breast cancer cell migration and invasion.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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, β-catenin and nuclear factor-κB (NF-κB) expression were determined using western blot technique. β-Catenin localization was observed by confocal microscopy.
  
  
  RESULTS
  We observed that high concentrations of GSE inhibited cell proliferation and apoptosis. Conversely, low GSE concentration decreased cell migration and invasion, likely by hampering β-catenin expression and localization, fascin and NF-κB expression, as well as by decreasing the activity of uPA, MMP-2 and MMP-9.
  
  
  CONCLUSIONS
  These results make GSE a powerful candidate for developing preventive agents against cancer metastasis.
authors.affiliation: Department of Clinical and Molecular Medicine, La Sapienza University, Piazza Sassari 3, 00161, Rome, Italy.
authors.forename: Simona
authors.initials: S
authors.lastname: Dinicola
authors.forename: Alessia
authors.initials: A
authors.lastname: Pasqualato
authors.forename: Alessandra
authors.initials: A
authors.lastname: Cucina
authors.forename: Pierpaolo
authors.initials: P
authors.lastname: Coluccia
authors.forename: Francesca
authors.initials: F
authors.lastname: Ferranti
authors.forename: Rita
authors.initials: R
authors.lastname: Canipari
authors.forename: Angela
authors.initials: A
authors.lastname: Catizone
authors.forename: Sara
authors.initials: S
authors.lastname: Proietti
authors.forename: Fabrizio
authors.initials: F
authors.lastname: D'Anselmi
authors.forename: Giulia
authors.initials: G
authors.lastname: Ricci
authors.forename: Alessandro
authors.initials: A
authors.lastname: Palombo
authors.forename: Mariano
authors.initials: M
authors.lastname: Bizzarri
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D001943:Breast Neoplasms / Q000737:chemistry / Q000473:pathology*; D002352:Carrier Proteins / Q000032:analysis; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D056604:Grape Seed Extract / Q000494:pharmacology*; D006801:Humans; D020782:Matrix Metalloproteinases / Q000187:drug effects / Q000378:metabolism; D008840:Microfilament Proteins / Q000032:analysis; D016328:NF-kappa B / Q000032:analysis; D009361:Neoplasm Invasiveness / Q000517:prevention & control*; D014568:Urokinase-Type Plasminogen Activator / Q000187:drug effects / Q000378:metabolism; D051176:beta Catenin / Q000032:analysis
chemical_list: D002352:Carrier Proteins; D056604:Grape Seed Extract; D008840:Microfilament Proteins; D016328:NF-kappa B; D051176:beta Catenin; C020324:fascin; D014568:Urokinase-Type Plasminogen Activator; D020782:Matrix Metalloproteinases