Preclinical anti-myeloma activity of the novel HDAC-inhibitor JNJ-26481585
- PMID: 20331455
- DOI: 10.1111/j.1365-2141.2010.08126.x
Preclinical anti-myeloma activity of the novel HDAC-inhibitor JNJ-26481585
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.
Similar articles
-
The novel inhibitor of histone deacetylase resminostat (RAS2410) inhibits proliferation and induces apoptosis in multiple myeloma (MM) cells.Br J Haematol. 2010 May;149(4):518-28. doi: 10.1111/j.1365-2141.2010.08124.x. Epub 2010 Mar 1. Br J Haematol. 2010. PMID: 20201941
-
The pan-histone deacetylase inhibitor CR2408 disrupts cell cycle progression, diminishes proliferation and causes apoptosis in multiple myeloma cells.Br J Haematol. 2012 Mar;156(5):633-42. doi: 10.1111/j.1365-2141.2011.08983.x. Epub 2011 Dec 23. Br J Haematol. 2012. PMID: 22211565
-
Histone deacetylase (HDAC) inhibitors as single agents induce multiple myeloma cell death principally through the inhibition of class I HDAC.Br J Haematol. 2013 Aug;162(4):559-62. doi: 10.1111/bjh.12388. Epub 2013 May 21. Br J Haematol. 2013. PMID: 23692150 No abstract available.
-
Panobinostat for the management of multiple myeloma.Future Oncol. 2017 Mar;13(6):477-488. doi: 10.2217/fon-2016-0329. Epub 2016 Oct 25. Future Oncol. 2017. PMID: 27776419 Review.
-
Targeting histone deacetylases: development of vorinostat for the treatment of cancer.Epigenomics. 2010 Jun;2(3):457-65. doi: 10.2217/epi.10.20. Epigenomics. 2010. PMID: 22121904 Review.
Cited by
-
Pan-Raf co-operates with PI3K-dependent signalling and critically contributes to myeloma cell survival independently of mutated RAS.Leukemia. 2017 Apr;31(4):922-933. doi: 10.1038/leu.2016.264. Epub 2016 Sep 30. Leukemia. 2017. PMID: 27686868
-
Loss of serum and glucocorticoid-regulated kinase 3 (SGK3) does not affect proliferation and survival of multiple myeloma cell lines.PLoS One. 2015 Apr 2;10(4):e0122689. doi: 10.1371/journal.pone.0122689. eCollection 2015. PLoS One. 2015. PMID: 25837824 Free PMC article.
-
Nano-Assembly of Quisinostat and Biodegradable Macromolecular Carrier Results in Supramolecular Complexes with Slow-Release Capabilities.Pharmaceutics. 2021 Nov 2;13(11):1834. doi: 10.3390/pharmaceutics13111834. Pharmaceutics. 2021. PMID: 34834249 Free PMC article.
-
The PI3K/Akt signaling pathway regulates the expression of Hsp70, which critically contributes to Hsp90-chaperone function and tumor cell survival in multiple myeloma.Haematologica. 2013 Jul;98(7):1132-41. doi: 10.3324/haematol.2012.066175. Epub 2012 Oct 12. Haematologica. 2013. PMID: 23065523 Free PMC article.
-
Epigenetic regulation in hematopoiesis and its implications in the targeted therapy of hematologic malignancies.Signal Transduct Target Ther. 2023 Feb 17;8(1):71. doi: 10.1038/s41392-023-01342-6. Signal Transduct Target Ther. 2023. PMID: 36797244 Free PMC article. Review.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical
