TY - JOUR A2 - Fulda, Simone AU - Rivera-Del Valle, Nilsa AU - Gao, Shan AU - Miller, Claudia P. AU - Fulbright, Joy AU - Gonzales, Carolina AU - Sirisawad, Mint AU - Steggerda, Susanne AU - Wheler, Jennifer AU - Balasubramanian, Sriram AU - Chandra, Joya PY - 2010 DA - 2010/01/18 TI - PCI-24781, a Novel Hydroxamic Acid HDAC Inhibitor, Exerts Cytotoxicity and Histone Alterations via Caspase-8 and FADD in Leukemia Cells SP - 207420 VL - 2010 AB - 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. SN - 1687-8876 UR - https://doi.org/10.1155/2010/207420 DO - 10.1155/2010/207420 JF - International Journal of Cell Biology PB - Hindawi Publishing Corporation KW - ER -