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Preclinical anti-myeloma activity of the novel HDAC-inhibitor JNJ-26481585
- Source :
- British journal of haematology. 149(4)
- Publication Year :
- 2010
-
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.
Details
- ISSN :
- 13652141
- Volume :
- 149
- Issue :
- 4
- Database :
- OpenAIRE
- Journal :
- British journal of haematology
- Accession number :
- edsair.pmid..........cce7c73e8fafa6eb173eb7a41038ac04