Title |
PCI-24781, a Novel Hydroxamic Acid HDAC Inhibitor, Exerts Cytotoxicity and Histone Alterations via Caspase-8 and FADD in Leukemia Cells
|
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Published in |
International Journal of Cell Biology, January 2010
|
DOI | 10.1155/2010/207420 |
Pubmed ID | |
Authors |
Nilsa Rivera-Del Valle, Shan Gao, Claudia P. Miller, Joy Fulbright, Carolina Gonzales, Mint Sirisawad, Susanne Steggerda, Jennifer Wheler, Sriram Balasubramanian, Joya Chandra |
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. |
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Unknown | 22 | 96% |
Demographic breakdown
Readers by professional status | Count | As % |
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Student > Master | 4 | 17% |
Researcher | 3 | 13% |
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Student > Bachelor | 1 | 4% |
Other | 3 | 13% |
Unknown | 4 | 17% |
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Neuroscience | 1 | 4% |
Other | 0 | 0% |
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