Cancer Chemotherapy and Pharmacology

, Volume 66, Issue 3, pp 611–616 | Cite as

The histone deacetylase inhibitor vorinostat induces calreticulin exposure in childhood brain tumour cells in vitro

  • Jürgen Sonnemann
  • Stephanie Greßmann
  • Sabine Becker
  • Susan Wittig
  • Mareike Schmudde
  • James F. Beck
Short Communication
First Online:
Received:
Accepted:

Abstract

Purpose

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.

Conclusion

Vorinostat has the capacity to elicit CRT exposure, suggesting its usefulness as immunogenic antitumour agent.

Keywords

Bortezomib Calreticulin Childhood brain tumour Histone deacetylase inhibitor TRAIL Vorinostat 

Abbreviations

CRT

Calreticulin

ER

Endoplasmatic reticulum

HDACi

Histone deacetylase inhibitor

sPNET

Supratentorial primitive neuroectodermal tumour

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Notes

Acknowledgments

We gratefully acknowledge the input and discussions of Barbara Bröker (Institute for Immunology, University of Greifswald). This work was supported by a grant from the “Wilhelm Sander-Stiftung, Neustadt/Donau”. S.G. received a fellowship from the “IZKF des Universitätsklinikum Jena”; M.S. received a fellowship from the “Alfried Krupp Wissenschaftskolleg Greifswald der Alfried Krupp von Bohlen und Halbach-Stiftung”.

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Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  • Jürgen Sonnemann
    • 1
    • 3
  • Stephanie Greßmann
    • 1
  • Sabine Becker
    • 1
  • Susan Wittig
    • 1
  • Mareike Schmudde
    • 2
  • James F. Beck
    • 1
  1. 1.Department of Paediatric Haematology and OncologyUniversity Children’s Hospital JenaJenaGermany
  2. 2.Institute for Immunology and Transfusion MedicineErnst Moritz Arndt UniversityGreifswaldGermany
  3. 3.Klinik für Kinder- und JugendmedizinFriedrich-Schiller-Universität JenaJenaGermany

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