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

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.

Titel: The histone deacetylase inhibitor SAHA acts in synergism with fenretinide and doxorubicin to control growth of rhabdoid tumor cells
Verfasser: Kerl, Kornelius Tobias GND
Ries, David
Unland, Rebecca
Borchert, Christiane
Moreno, Natalia GND
Hasselblatt, Martin GND
Jürgens, Heribert GND
Kool, Marcel GND
Görlich, Dennis GND
Eveslage, Maria
Jung, Manfred
Meisterernst, Michael
Frühwald, Michael
Organisation: FB 05: Medizinische Fakultät
FB 12: Chemie und Pharmazie
Dokumenttyp: Artikel
Medientyp: Text
Erscheinungsdatum: 13.06.2013
Publikation in MIAMI: 24.02.2014
Datum der letzten Änderung: 16.04.2019
Quelle: BMC Cancer 13 (2013) 286
Fachgebiete: Medizin und Gesundheit
Lizenz: CC BY 2.0
Sprache: Englisch
Anmerkungen: Finanziert durch den Open-Access-Publikationsfonds 2013/2014 der Deutschen Forschungsgemeinschaft (DFG) und der Westfälischen Wilhelms-Universität Münster (WWU Münster).
Format: PDF-Dokument
URN: urn:nbn:de:hbz:6-94309669593
Permalink: https://nbn-resolving.org/urn:nbn:de:hbz:6-94309669593
DOI: 10.1186/1471-2407-13-286
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