Abstract |
Pharmacological inhibitors of histone deacetylases (HDACs) are currently being developed and tested as anti- cancer agents and may be useful to enhance the therapeutic efficiency of established anti-myeloma treatments. This study preclinically evaluated the effects of the 'second generation' pan- HDAC inhibitor JNJ-26481585 on human multiple myeloma (MM) cells from established cell lines and primary MM samples (n=42). Molecular responses in both groups of MM cells included histone acetylation, a shift in Bcl2-family members towards proapoptotic bias, attenuation of growth and survival pathway activity and Hsp72 induction. Mcl-1 depletion and Hsp72 induction were the most reliable features observed in JNJ-26481585-treated primary MM samples. The drug alone effectively induced myeloma cell death at low nanomolar concentrations. In vitro combination of JNJ-26481585 with anti-myeloma therapeutic agents generally resulted In effects close to additivity. In view of the favourable activity of this novel HDAC-inhibitor towards primary myeloma cells further evaluation in a clinical setting is warranted.
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Authors | Thorsten Stühmer, Janine Arts, Manik Chatterjee, Johanna Borawski, André Wolff, Peter King, Hermann Einsele, Eugen Leo, Ralf C Bargou |
Journal | British journal of haematology
(Br J Haematol)
Vol. 149
Issue 4
Pg. 529-36
(May 2010)
ISSN: 1365-2141 [Electronic] England |
PMID | 20331455
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antineoplastic Agents
- Histone Deacetylase Inhibitors
- Histones
- Hydroxamic Acids
- quisinostat
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Topics |
- Acetylation
(drug effects)
- Antineoplastic Agents
(pharmacology)
- Antineoplastic Combined Chemotherapy Protocols
(pharmacology)
- Apoptosis
(drug effects)
- Dose-Response Relationship, Drug
- Drug Evaluation, Preclinical
(methods)
- Histone Deacetylase Inhibitors
(pharmacology)
- Histones
(metabolism)
- Humans
- Hydroxamic Acids
(pharmacology)
- Multiple Myeloma
(metabolism, pathology)
- Tumor Cells, Cultured
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