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...
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| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2010-01-01
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| Series: | International Journal of Cell Biology |
| Online Access: | http://dx.doi.org/10.1155/2010/207420 |
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| author | Nilsa Rivera-Del Valle Shan Gao Claudia P. Miller Joy Fulbright Carolina Gonzales Mint Sirisawad Susanne Steggerda Jennifer Wheler Sriram Balasubramanian Joya Chandra |
| author_facet | Nilsa Rivera-Del Valle Shan Gao Claudia P. Miller Joy Fulbright Carolina Gonzales Mint Sirisawad Susanne Steggerda Jennifer Wheler Sriram Balasubramanian Joya Chandra |
| author_sort | Nilsa Rivera-Del Valle |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-684e885e38f248eaadb4ac4276f1250e |
| institution | OA Journals |
| issn | 1687-8876 1687-8884 |
| language | English |
| publishDate | 2010-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | International Journal of Cell Biology |
| spelling | doaj-art-684e885e38f248eaadb4ac4276f1250e2025-08-20T02:06:40ZengWileyInternational Journal of Cell Biology1687-88761687-88842010-01-01201010.1155/2010/207420207420PCI-24781, a Novel Hydroxamic Acid HDAC Inhibitor, Exerts Cytotoxicity and Histone Alterations via Caspase-8 and FADD in Leukemia CellsNilsa Rivera-Del Valle0Shan Gao1Claudia P. Miller2Joy Fulbright3Carolina Gonzales4Mint Sirisawad5Susanne Steggerda6Jennifer Wheler7Sriram Balasubramanian8Joya Chandra9Department of Pediatrics Research, Children's Cancer Hospital, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USADepartment of Pediatrics Research, Children's Cancer Hospital, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USADepartment of Pediatrics Research, Children's Cancer Hospital, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USADepartment of Pediatrics Research, Children's Cancer Hospital, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USADepartment of Pediatrics Research, Children's Cancer Hospital, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USAPharmacyclics Inc., Sunnyvale, CA 94085, USAPharmacyclics Inc., Sunnyvale, CA 94085, USADepartment of Investigational Therapeutics, The University of Texas M. D. Anderson Children's Cancer Hospital, Houston, TX 77030, USAPharmacyclics Inc., Sunnyvale, CA 94085, USADepartment of Pediatrics Research, Children's Cancer Hospital, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USAHistone 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.http://dx.doi.org/10.1155/2010/207420 |
| spellingShingle | Nilsa Rivera-Del Valle Shan Gao Claudia P. Miller Joy Fulbright Carolina Gonzales Mint Sirisawad Susanne Steggerda Jennifer Wheler Sriram Balasubramanian Joya Chandra PCI-24781, a Novel Hydroxamic Acid HDAC Inhibitor, Exerts Cytotoxicity and Histone Alterations via Caspase-8 and FADD in Leukemia Cells International Journal of Cell Biology |
| title | PCI-24781, a Novel Hydroxamic Acid HDAC Inhibitor, Exerts Cytotoxicity and Histone Alterations via Caspase-8 and FADD in Leukemia Cells |
| title_full | PCI-24781, a Novel Hydroxamic Acid HDAC Inhibitor, Exerts Cytotoxicity and Histone Alterations via Caspase-8 and FADD in Leukemia Cells |
| title_fullStr | PCI-24781, a Novel Hydroxamic Acid HDAC Inhibitor, Exerts Cytotoxicity and Histone Alterations via Caspase-8 and FADD in Leukemia Cells |
| title_full_unstemmed | PCI-24781, a Novel Hydroxamic Acid HDAC Inhibitor, Exerts Cytotoxicity and Histone Alterations via Caspase-8 and FADD in Leukemia Cells |
| title_short | PCI-24781, a Novel Hydroxamic Acid HDAC Inhibitor, Exerts Cytotoxicity and Histone Alterations via Caspase-8 and FADD in Leukemia Cells |
| title_sort | pci 24781 a novel hydroxamic acid hdac inhibitor exerts cytotoxicity and histone alterations via caspase 8 and fadd in leukemia cells |
| url | http://dx.doi.org/10.1155/2010/207420 |
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