title: Sanguisorba minor extract suppresses plasmin-mediated mechanisms of cancer cell migration.
abstract: BACKGROUND
  Sanguisorba minor, as well as several other edible herbs and vegetables, has been used extensively in traditional medicine. The observed beneficial effects can be attributed at least in part to the direct modulation of several enzymatic activities by its polyphenolic constituents.
  
  
  METHODS
  The ethanol extract of Sanguisorba minor was characterized by reversed-phase liquid chromatography, and most relevant analytes were identified by multiple stage mass spectrometry. The whole extract and the most relevant isolated constituents were tested for their ability to modulate the activity of human plasmin both toward a synthetic substrate and in human breast cancer cell culture models. Kinetic and equilibrium parameters were obtained by a concerted spectrophotometric and biosensor-based approach.
  
  
  RESULTS
  Quercetin-3-glucuronide was recognized as the compound mainly responsible for the in vitro plasmin inhibition by S. minor extract, with an inhibition constant in the high nanomolar range; in detail, our approach based on bioinformatic, enzymatic and binding analyses classified the inhibition as competitive. Most interestingly, cell-based assays showed that this flavonoid was effective in suppressing plasmin-induced loss of cancer cell adhesion.
  
  
  CONCLUSIONS
  Our results show that the extract from Sanguisorba minor limits plasmin-mediated tumor cell motility in vitro, mostly due to quercetin-3-glucuronide. This glucuronated flavonoid is a promising template for rational designing of anticancer drugs to be used in the treatment of pathological states involving the unregulated activity of plasmin.
authors.affiliation: School of Biosciences and Biotechnology, University of Camerino, Camerino, Italy. massimiliano.cuccioloni@unicam.it
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Cuccioloni
authors.forename: Laura
authors.initials: L
authors.lastname: Bonfili
authors.forename: Matteo
authors.initials: M
authors.lastname: Mozzicafreddo
authors.forename: Valentina
authors.initials: V
authors.lastname: Cecarini
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Eleuteri
authors.forename: Mauro
authors.initials: M
authors.lastname: Angeletti
mesh_terms: D015374:Biosensing Techniques; D002448:Cell Adhesion / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects*; D002851:Chromatography, High Pressure Liquid; D005341:Fibrinolysin / Q000037:antagonists & inhibitors / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D010936:Plant Extracts / Q000302:isolation & purification / Q000494:pharmacology*; D011487:Protein Conformation; D011794:Quercetin / Q000031:analogs & derivatives* / Q000302:isolation & purification / Q000494:pharmacology; D031993:Sanguisorba / Q000737:chemistry*
chemical_list: D010936:Plant Extracts; C443401:quercetin 3-O-glucuronide; D011794:Quercetin; D005341:Fibrinolysin