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BMC Cancer
Published in: BMC Cancer 1/2013

Open Access 01-12-2013 | Research article

The histone deacetylase inhibitor SAHA acts in synergism with fenretinide and doxorubicin to control growth of rhabdoid tumor cells

Authors: Kornelius Kerl, David Ries, Rebecca Unland, Christiane Borchert, Natalia Moreno, Martin Hasselblatt, Heribert Jürgens, Marcel Kool, Dennis Görlich, Maria Eveslage, Manfred Jung, Michael Meisterernst, Michael Frühwald

Published in: BMC Cancer | Issue 1/2013

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Abstract

Background

Rhabdoid tumors are highly aggressive malignancies affecting infants and very young children. In many instances these tumors are resistant to conventional type chemotherapy necessitating alternative approaches.

Methods

Proliferation assays (MTT), apoptosis (propidium iodide/annexin V) and cell cycle analysis (DAPI), RNA expression microarrays and western blots were used to identify synergism of the HDAC (histone deacetylase) inhibitor SAHA with fenretinide, tamoxifen and doxorubicin in rhabdoidtumor cell lines.

Results

HDAC1 and HDAC2 are overexpressed in primary rhabdoid tumors and rhabdoid tumor cell lines. Targeting HDACs in rhabdoid tumors induces cell cycle arrest and apoptosis. On the other hand HDAC inhibition induces deregulated gene programs (MYCC-, RB program and the stem cell program) in rhabdoid tumors. These programs are in general associated with cell cycle progression. Targeting these activated pro-proliferative genes by combined approaches of HDAC-inhibitors plus fenretinide, which inhibits cyclinD1, exhibit strong synergistic effects on induction of apoptosis. Furthermore, HDAC inhibition sensitizes rhabdoid tumor cell lines to cell death induced by chemotherapy.

Conclusion

Our data demonstrate that HDAC inhibitor treatment in combination with fenretinide or conventional chemotherapy is a promising tool for the treatment of chemoresistant rhabdoid tumors.
Appendix
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Metadata
Title
The histone deacetylase inhibitor SAHA acts in synergism with fenretinide and doxorubicin to control growth of rhabdoid tumor cells
Authors
Kornelius Kerl
David Ries
Rebecca Unland
Christiane Borchert
Natalia Moreno
Martin Hasselblatt
Heribert Jürgens
Marcel Kool
Dennis Görlich
Maria Eveslage
Manfred Jung
Michael Meisterernst
Michael Frühwald
Publication date
01-12-2013
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2013
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/1471-2407-13-286

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