AT-101 ( R -(−)-gossypol acetic acid) enhances the effectiveness of androgen deprivation therapy in the VCaP prostate cancer model
dc.contributor.author | McGregor, Natalie | en_US |
dc.contributor.author | Patel, Lalit R. | en_US |
dc.contributor.author | Craig, Matthew J. | en_US |
dc.contributor.author | Weidner, Savannah | en_US |
dc.contributor.author | Wang, Shaomeng | en_US |
dc.contributor.author | Pienta, Kenneth J. | en_US |
dc.date.accessioned | 2010-08-02T17:47:18Z | |
dc.date.available | 2011-03-01T16:26:48Z | en_US |
dc.date.issued | 2010-08-01 | en_US |
dc.identifier.citation | McGregor, Natalie; Patel, Lalit; Craig, Matthew; Weidner, Savannah; Wang, Shaomeng; Pienta, Kenneth J. (2010). "AT-101 ( R -(−)-gossypol acetic acid) enhances the effectiveness of androgen deprivation therapy in the VCaP prostate cancer model." Journal of Cellular Biochemistry 110(5): 1187-1194. <http://hdl.handle.net/2027.42/77515> | en_US |
dc.identifier.issn | 0730-2312 | en_US |
dc.identifier.issn | 1097-4644 | en_US |
dc.identifier.uri | https://hdl.handle.net/2027.42/77515 | |
dc.description.abstract | Prostate cancer remains a leading cause of cancer death in American men. Androgen deprivation therapy (ADT) is the most common treatment for advanced prostate cancer patients; however, ADT fails in nearly all cases resulting in castration resistant or androgen-insensitive (AI) disease. In many cases, this progression results from dysregulation of the pro-survival Bcl-2 family proteins. Inhibition of pro-survival Bcl-2 family proteins, therefore, may be an effective strategy to delay the onset of AI disease. Gossypol, a small molecule inhibitor of pro-survival Bcl-2 family proteins, has been demonstrated to inhibit AI prostate cancer growth. The apoptotic effect of gossypol, however, has been demonstrated to be attenuated by the presence of androgen in a prostate cancer xenograft mouse model (Vertebral Cancer of Prostate [VCaP]) treated with AT-101 ( R -(−)-gossypol acetic acid). This study was undertaken to better understand the in vitro effects of androgen receptor (AR) on AT-101-induced apoptosis. VCaP cells treated with AT-101 demonstrated an increase in apoptosis and downregulation of Bcl-2 pro-survival proteins. Upon AR activation in combination with AT-101 treatment, apoptosis is reduced, cell survival increases, and caspase activation is attenuated. Akt and X inhibitor of apoptosis (XIAP) are downregulated in the presence of AT-101, and AR stimulation rescues protein expression. Combination treatment of bicalutamide and AT-101 increases apoptosis by reducing the expression of these pro-survival proteins. These data suggest that combination therapy of AT-101 and ADT may further delay the onset of AI disease, resulting in prolonged progression-free survival of prostate cancer patients. J. Cell. Biochem. 110: 1187–1194, 2010. Published 2010 Wiley-Liss, Inc. | en_US |
dc.format.extent | 2880094 bytes | |
dc.format.extent | 3118 bytes | |
dc.format.mimetype | application/pdf | |
dc.format.mimetype | text/plain | |
dc.publisher | Wiley Subscription Services, Inc., A Wiley Company | en_US |
dc.subject.other | Life and Medical Sciences | en_US |
dc.subject.other | Cell & Developmental Biology | en_US |
dc.title | AT-101 ( R -(−)-gossypol acetic acid) enhances the effectiveness of androgen deprivation therapy in the VCaP prostate cancer model | en_US |
dc.type | Article | en_US |
dc.rights.robots | IndexNoFollow | en_US |
dc.subject.hlbsecondlevel | Genetics | en_US |
dc.subject.hlbsecondlevel | Molecular, Cellular and Developmental Biology | en_US |
dc.subject.hlbtoplevel | Health Sciences | en_US |
dc.subject.hlbtoplevel | Science | en_US |
dc.description.peerreviewed | Peer Reviewed | en_US |
dc.contributor.affiliationum | Department of Internal Medicine, University of Michigan School of Medicine, Ann Arbor, Michigan | en_US |
dc.contributor.affiliationum | Department of Internal Medicine, University of Michigan School of Medicine, Ann Arbor, Michigan | en_US |
dc.contributor.affiliationum | Department of Internal Medicine, University of Michigan School of Medicine, Ann Arbor, Michigan | en_US |
dc.contributor.affiliationum | Department of Internal Medicine, University of Michigan School of Medicine, Ann Arbor, Michigan | en_US |
dc.contributor.affiliationum | Department of Internal Medicine, University of Michigan School of Medicine, Ann Arbor, Michigan ; University of Michigan Comprehensive Cancer Center, Ann Arbor, Michigan | en_US |
dc.contributor.affiliationum | Department of Internal Medicine, University of Michigan School of Medicine, Ann Arbor, Michigan ; University of Michigan Comprehensive Cancer Center, Ann Arbor, Michigan ; Department of Urology, University of Michigan School of Medicine, Ann Arbor, Michigan ; Michigan Center for Translational Pathology, Ann Arbor, Michigan ; 1500 E. Medical Center Drive, 7303 Cancer Center, Ann Arbor, MI 48109-5946. | en_US |
dc.identifier.pmid | 20589722 | en_US |
dc.description.bitstreamurl | http://deepblue.lib.umich.edu/bitstream/2027.42/77515/1/22633_ftp.pdf | |
dc.identifier.doi | 10.1002/jcb.22633 | en_US |
dc.identifier.source | Journal of Cellular Biochemistry | en_US |
dc.owningcollname | Interdisciplinary and Peer-Reviewed |
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