title: The histone deacetylase inhibitor vorinostat induces calreticulin exposure in childhood brain tumour cells in vitro.
abstract: OBJECTIVE
  It has recently been recognised that anticancer chemotherapy can elicit an immunogenic form of apoptosis characterised by the exposure of calreticulin (CRT) on the surface of dying tumour cells, entailing an immune response that contributes to the therapeutic outcome. CRT exposure has been found to be induced by anthracyclins and oxaliplatin, but not by other proapoptotic antineoplastic agents including etoposide, camptothecin and cisplatin. In this study, we examined the histone deacetylase inhibitor vorinostat for its capability to stimulate CRT exposure in tumour cells.
  
  
  METHODS
  Childhood tumour cells, i.e. the brain tumour cell lines PFSK and DAOY and the Ewing's sarcoma cell line CADO-ES-1, were treated with vorinostat, and CRT exposure was determined by flow cytometric analysis of CRT immunofluorescence. Combination effects of vorinostat/TRAIL and vorinostat/bortezomib were also assessed.
  
  
  RESULTS
  Vorinostat treatment induced CRT exposure in PFSK and DAOY cells, but not in caspase-8-deficient CADO-ES-1 cells. CRT exposure could be prevented by the pan-caspase inhibitor z-VAD-fmk and by brefeldin A, an inhibitor of Golgi-mediated transport.
  
  
  CONCLUSIONS
  Vorinostat has the capacity to elicit CRT exposure, suggesting its usefulness as immunogenic antitumour agent.
authors.affiliation: Department of Paediatric Haematology and Oncology, University Children's Hospital Jena, Jena, Germany. juergen.sonnemann@med.uni-jena.de
authors.forename: Jürgen
authors.initials: J
authors.lastname: Sonnemann
authors.forename: Stephanie
authors.initials: S
authors.lastname: Gressmann
authors.forename: Sabine
authors.initials: S
authors.lastname: Becker
authors.forename: Susan
authors.initials: S
authors.lastname: Wittig
authors.forename: Mareike
authors.initials: M
authors.lastname: Schmudde
authors.forename: James F
authors.initials: JF
authors.lastname: Beck
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D001897:Boronic Acids / Q000494:pharmacology; D000069286:Bortezomib; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000473:pathology; D037282:Calreticulin / Q000187:drug effects* / Q000378:metabolism; D053181:Caspase 8 / Q000378:metabolism; D045744:Cell Line, Tumor; D002648:Child; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique / Q000379:methods; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology*; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology*; D011719:Pyrazines / Q000494:pharmacology; D000077337:Vorinostat
chemical_list: D000970:Antineoplastic Agents; D001897:Boronic Acids; D037282:Calreticulin; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D011719:Pyrazines; D000077337:Vorinostat; D000069286:Bortezomib; D053181:Caspase 8