PCI-24781, a Novel Hydroxamic Acid HDAC Inhibitor, Exerts Cytotoxicity and Histone Alterations via Caspase-8 and FADD in Leukemia Cells.

Int J Cell Biol 2010 18;2010:207420. Epub 2010 Jan 18.

Department of Pediatrics Research, Children's Cancer Hospital, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA.

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.

Download full-text PDF

Source
http://dx.doi.org/10.1155/2010/207420DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2817379PMC
February 2010
20 Reads

Publication Analysis

Top Keywords

histone alterations
12
leukemia cells
8
caspase-8 fadd
8
superoxide levels
8
hdac inhibitor
8
pci-24781 novel
8
novel hydroxamic
8
apoptosis induction
8
pci-24781
6
histone
5
acute leukemia
4
fadd acute
4
reported hdaci
4
pci-24781 treatment
4
domain fadd
4
treatment increase
4
levels reported
4
increase superoxide
4
cells pci-24781
4
molecule fas-associated
4

Similar Publications