title: Synergistic killing of glioblastoma stem-like cells by bortezomib and HDAC inhibitors.
abstract: BACKGROUND
  The malignant brain tumour glioblastoma is a devastating disease that remains a therapeutic challenge.
  
  
  METHODS
  Effects of combinations of the US Food and Drug Administation (FDA) approved proteasome inhibitor bortezomib and the histone deacetylase (HDAC) inhibitors vorinostat, valproic acid and sodium phenylbutyrate were studied on primary glioblastoma stem cell lines and conventional glioblastoma cell lines. Cell survival, proliferation and death were analyzed by fluorometric microculture cytotoxicity assay (FMCA), propidium iodide labeling and flow cytometry, and cell cloning through limiting dilution and live-cell bright-field microscopy.
  
  
  RESULTS
  Bortezomib and the HDAC inhibitors showed synergistic cell killing at clinically relevant drug concentrations, while the conventional cell lines cultured in serum-containing medium were relatively resistant to the same treatments.
  
  
  CONCLUSIONS
  These findings of synergistic glioblastoma stem cell killing by bortezomib and three different FDA-approved HDAC inhibitors confirm and expand previous observations on co-operative effects between these classes of drugs.
authors: Department of Radiation Sciences and Oncology, Umeå University, SE-90187, Umeå, Sweden. thomas.asklund@onkologi.umu.se
authors: Thomas
authors: T
authors: Asklund
authors: Samuel
authors: S
authors: Kvarnbrink
authors: Camilla
authors: C
authors: Holmlund
authors: Carl
authors: C
authors: Wibom
authors: Tommy
authors: T
authors: Bergenheim
authors: Roger
authors: R
authors: Henriksson
authors: Håkan
authors: H
authors: Hedman
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001897:Boronic Acids / Q000008:administration & dosage / Q000494:pharmacology*; D000069286:Bortezomib; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000473:pathology; D045744:Cell Line, Tumor; D004357:Drug Synergism; D005909:Glioblastoma / Q000188:drug therapy* / Q000473:pathology; D056572:Histone Deacetylase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D006877:Hydroxamic Acids / Q000008:administration & dosage / Q000494:pharmacology; D014411:Neoplastic Stem Cells / Q000187:drug effects* / Q000473:pathology; D058953:Neural Stem Cells / Q000187:drug effects* / Q000473:pathology; D010654:Phenylbutyrates / Q000008:administration & dosage / Q000494:pharmacology; D011719:Pyrazines / Q000008:administration & dosage / Q000494:pharmacology*; D014635:Valproic Acid / Q000008:administration & dosage / Q000494:pharmacology; D000077337:Vorinostat
chemical_list: D001897:Boronic Acids; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D010654:Phenylbutyrates; D011719:Pyrazines; D000077337:Vorinostat; D014635:Valproic Acid; D000069286:Bortezomib