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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
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...
Autores principales: | , , , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
Publicado: |
Hindawi Publishing Corporation
2010
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2817379/ https://www.ncbi.nlm.nih.gov/pubmed/20145726 http://dx.doi.org/10.1155/2010/207420 |
Sumario: | 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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