title: Anti-proliferative and anti-migration effects of Polish propolis combined with Hypericum perforatum L. on glioblastoma multiforme cell line U87MG.
abstract: BACKGROUND
  Propolis and Hypericum perforatum L. are natural products which contain many active compounds and have numerous beneficial effects, including an antitumor effect. Gliobmastoma multiforme (GBM) is a common primary brain tumor with poor prognosis and limited treatment options. In this study, the effect of propolis (EEP) combined with H. perforatum L. (HPE) on glioblastoma cell line U87MG was investigated for the first time.
  
  
  METHODS
  Anti-proliferative activity of EEP, HPE and their combination (EEP + HPE) was determined by a cytotoxicity test, DNA binding by [(3)H]-thymidine incorporation and cell migration assay. Anti-metastatic properties in U87MG treated with EEP, HPE and EEP + HPE were estimated on cells migration test (scratch assay) and metalloproteinases (MMP2 and MMP9) secretion (gelatin zymography).
  
  
  RESULTS
  Combination of HPE and EEP extracts was found to have a time- and dose-dependent inhibitory effect on the viability of U87MG cells. This effect was significantly higher (p < 0.05) when compared to these two extracts applied separately, which was confirmed by the significant reduction of DNA synthesis and significantly higher mitochondrial membrane permeabilization. A significant decreasing in migration cells and in pro-MMP9 and pro-MMP2 secretion in U87MG cells were demonstrated after exposure to combination of EEP (30 μg/ml) with HPE (6.25 μg/ml).
  
  
  CONCLUSIONS
  In this study, the combination of ethanolic extract from propolis and ethanolic extract of fresh-cut H. perforatum L. was proved the ability to reduce invasiveness of glioma cells through the inhibition of MMP2 and MMP9 secretion and suppression of cell migration. It has a more potent anti-proliferative effect on U87MG glioma cell line compared to using propolis and H. perforatum L. separately. Further studies are required to verify whether the examined extracts can activate apoptotic pathways.
authors.affiliation: Department of Bromatology, Faculty of Pharmacy with Division of Laboratory Medicine, Medical University of Bialystok, Mickiewicza 2D, 15-222, Bialystok, Poland. bromatos@umb.edu.pl.
authors.forename: Maria H
authors.initials: MH
authors.lastname: Borawska
authors.affiliation: Department of Bromatology, Faculty of Pharmacy with Division of Laboratory Medicine, Medical University of Bialystok, Mickiewicza 2D, 15-222, Bialystok, Poland.
authors.forename: Sylwia K
authors.initials: SK
authors.lastname: Naliwajko
authors.affiliation: Department of Bromatology, Faculty of Pharmacy with Division of Laboratory Medicine, Medical University of Bialystok, Mickiewicza 2D, 15-222, Bialystok, Poland.
authors.forename: Justyna
authors.initials: J
authors.lastname: Moskwa
authors.affiliation: Department of Bromatology, Faculty of Pharmacy with Division of Laboratory Medicine, Medical University of Bialystok, Mickiewicza 2D, 15-222, Bialystok, Poland.
authors.forename: Renata
authors.initials: R
authors.lastname: Markiewicz-Żukowska
authors.affiliation: Department of Bromatology, Faculty of Pharmacy with Division of Laboratory Medicine, Medical University of Bialystok, Mickiewicza 2D, 15-222, Bialystok, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Puścion-Jakubik
authors.affiliation: Department of Bromatology, Faculty of Pharmacy with Division of Laboratory Medicine, Medical University of Bialystok, Mickiewicza 2D, 15-222, Bialystok, Poland.
authors.forename: Jolanta
authors.initials: J
authors.lastname: Soroczyńska
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D005909:Glioblastoma; D006801:Humans; D020902:Hypericum / Q000737:chemistry*; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D011429:Propolis / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D010936:Plant Extracts; D011429:Propolis
keywords: Glioblastoma multiforme; H. perforatum L.; Propolis