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PCI-24781, a Novel Hydroxamic Acid HDAC Inhibitor, Exerts Cytotoxicity and Histone Alterations via Caspase-8 and FADD in Leukemia Cells
- Source :
- International Journal of Cell Biology, Vol 2010 (2010)
- Publication Year :
- 2010
- Publisher :
- Wiley, 2010.
-
Abstract
- Histone deacetylase inhibitors (HDACi) have become a promising new avenue for cancer therapy, and many are currently in Phase I/II clinical trials for various tumor types. In the present study, we show that apoptosis induction and histone alterations by PCI-24781, a novel hydroxamic acid-based HDAC inhibitor, require caspase-8 and the adaptor molecule, Fas-associated death domain (FADD), in acute leukemia cells. PCI-24781 treatment also causes an increase in superoxide levels, which has been reported for other HDACi. However, an antioxidant does not reverse histone alterations caused by PCI-24781, indicating that ROS generation is likely downstream of the effects that PCI-24781 exerts on histone H3. Taken together, these results provide insight into the mechanism of apoptosis induction by PCI-24781 in leukemia by highlighting the roles of caspase-8, FADD and increased superoxide levels.
Details
- Language :
- English
- ISSN :
- 16878876 and 16878884
- Volume :
- 2010
- Database :
- Directory of Open Access Journals
- Journal :
- International Journal of Cell Biology
- Publication Type :
- Academic Journal
- Accession number :
- edsdoj.684e885e38f248eaadb4ac4276f1250e
- Document Type :
- article
- Full Text :
- https://doi.org/10.1155/2010/207420