Trichostatin A restores Apaf-1 function in chemoresistant ovarian cancer cells
dc.contributor.author | Tan, Lijun | en_US |
dc.contributor.author | Kwok, Roland P. | en_US |
dc.contributor.author | Shukla, Abhishek | en_US |
dc.contributor.author | Kshirsagar, Malti | en_US |
dc.contributor.author | Zhao, Lili | en_US |
dc.contributor.author | Opipari, Anthony W. | en_US |
dc.contributor.author | Liu, J. Rebecca | en_US |
dc.date.accessioned | 2011-03-10T16:03:42Z | |
dc.date.accessioned | 2011-03-10T16:03:42Z | |
dc.date.available | 2012-04-03T21:46:58Z | en_US |
dc.date.issued | 2011-02-15 | en_US |
dc.identifier.citation | Tan, Lijun; Kwok, Roland P.; Shukla, Abhishek; Kshirsagar, Malti; Zhao, Lili; Opipari, Anthony W.; Liu, J. Rebecca (2011). "Trichostatin A restores Apaf-1 function in chemoresistant ovarian cancer cells." Cancer 117(4): 784-794. <http://hdl.handle.net/2027.42/83214> | en_US |
dc.identifier.issn | 0008-543X | en_US |
dc.identifier.issn | 1097-0142 | en_US |
dc.identifier.uri | https://hdl.handle.net/2027.42/83214 | |
dc.description.abstract | BACKGROUND: Chemoresistance is the major factor limiting long-term treatment success in patients with epithelial ovarian cancers. Most cytotoxic drugs kill cells through apoptosis; therefore, defective execution of apoptotic pathways results in a drug-resistant phenotype in many tumor types. METHODS: A panel of ovarian cancer cell lines was screened for expression and function of the apoptosome components Apaf-1 and caspase-9. Expression levels were analyzed by immunohistochemistry and immunoblotting; Apaf-1 function was determined by assessing the ability of endogenous Apaf-1 to cleave caspase-9 in the presence or absence of cytochrome c . The effect of the histone deacetylase inhibitor trichostatin A on Apaf-1 expression and function was evaluated. RESULTS: The authors report here that the resistance of ovarian cancer cells to the proapoptotic effects of chemotherapy is due in part to deficient Apaf-1 activity. Although Apaf-1 is expressed in most ovarian cancers, the functional activity is impaired, as Apaf-1 has a diminished ability to recruit and activate caspase-9. Treatment of ovarian cancer cells with trichostatin A results in restoration of Apaf-1 function independent of alterations in Apaf-1 expression. Furthermore, treating chemoresistant cells with sublethal doses of trichostatin A restores Apaf-1 function and sensitizes cells to cisplatin-induced apoptosis. CONCLUSIONS: Targeting intrinsic pathway defects for therapeutic intervention may result in sensitizing tumors to standard chemotherapy or triggering apoptosis in the absence of other apoptotic signals. The identification of drugs that can use Apaf-1 when it is present, yet can overcome its functional inactivation, may be an important clinical advance. Cancer 2011. © 2010 American Cancer Society. | en_US |
dc.publisher | Wiley Subscription Services, Inc., A Wiley Company | en_US |
dc.subject.other | Life and Medical Sciences | en_US |
dc.subject.other | Cancer Research, Oncology and Pathology | en_US |
dc.title | Trichostatin A restores Apaf-1 function in chemoresistant ovarian cancer cells | en_US |
dc.type | Article | en_US |
dc.rights.robots | IndexNoFollow | en_US |
dc.subject.hlbsecondlevel | Oncology and Hematology | en_US |
dc.subject.hlbsecondlevel | Public Health | en_US |
dc.subject.hlbtoplevel | Health Sciences | en_US |
dc.description.peerreviewed | Peer Reviewed | en_US |
dc.contributor.affiliationum | Department of Obstetrics and Gynecology, University of Michigan Comprehensive Cancer Center, Ann Arbor, Michigan | en_US |
dc.contributor.affiliationum | Department of Obstetrics and Gynecology, University of Michigan Comprehensive Cancer Center, Ann Arbor, Michigan | en_US |
dc.contributor.affiliationum | Department of Pathology, University of Michigan Comprehensive Cancer Center, Ann Arbor, Michigan | en_US |
dc.contributor.affiliationum | Department of Pathology, University of Michigan Comprehensive Cancer Center, Ann Arbor, Michigan | en_US |
dc.contributor.affiliationum | Biostatistics Unit, University of Michigan Comprehensive Cancer Center, Ann Arbor, Michigan | en_US |
dc.contributor.affiliationum | Department of Obstetrics and Gynecology, University of Michigan Comprehensive Cancer Center, Ann Arbor, Michigan | en_US |
dc.contributor.affiliationum | Department of Obstetrics and Gynecology, University of Michigan Comprehensive Cancer Center, Ann Arbor, Michigan ; Fax: (734) 764-7261 ; Department of Obstetrics and Gynecology, University of Michigan Comprehensive Cancer Center, L4510 WH, 1500 East Medical Center Drive, Ann Arbor, MI 48109 | en_US |
dc.identifier.pmid | 20925046 | en_US |
dc.description.bitstreamurl | http://deepblue.lib.umich.edu/bitstream/2027.42/83214/1/25649_ftp.pdf | |
dc.identifier.doi | 10.1002/cncr.25649 | en_US |
dc.identifier.source | Cancer | en_US |
dc.owningcollname | Interdisciplinary and Peer-Reviewed |
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