Abstract:
:TPCK is widely used as an inhibitor of chymotrypsin-like proteases but has recently been identified as an inhibitor of the PDK1/Akt pathway. In this study, we show that TPCK inhibits TRAIL-induced caspase activity but potentiates wortmannin-dependent caspase activity in prostatic carcinoma cell lines. The inhibitory activity of TPCK was found to be death ligand-specific since TPCK inhibits TRAIL-mediated caspase activity but does not affect Fas-induced caspase activity. Our data also show that impaired TRAIL-DISC formation in the presence of TPCK is responsible for caspase inhibition. Further, TPCK induces p53 expression and inhibits the PDK1/Akt pathway resulting in BAD dephosphorylation, and the release of cytochrome c and Smac/DIABLO from mitochondria. TPCK also selectively decreases the levels of androgen receptor and caspase-2 whereas it does not change the levels of other proteins (caspases-3, -7, -8, -9; heat shock proteins 27, 70, 90). Finally, TPCK-induced degradation of caspase-2 is protected by Bcl-2 overexpression, apparently by an adapter protein since direct interaction between caspase-2 and Bcl-2 was not detected. Together, these features suggest that TPCK could be used as a therapeutic agent for treatment of those tumor cells that are resistant to ligand-induced treatment because of aberrant signaling pathways downstream of the DISC.
journal_name
Cancer Biol Therjournal_title
Cancer biology & therapyauthors
Rokhlin OW,Guseva NV,Taghiyev AF,Glover RA,Cohen MBdoi
10.4161/cbt.3.8.970keywords:
subject
Has Abstractpub_date
2004-08-01 00:00:00pages
761-8issue
8eissn
1538-4047issn
1555-8576pii
970journal_volume
3pub_type
杂志文章abstract::Cancer cells convert glucose preferentially to lactate even in the presence of oxygen (aerobic glycolysis-Warburg effect). New concepts in cancer treatment aim at inhibition of aerobic glycolysis. Pyruvate dehydrogenase converts pyruvate to acetylCoA thus preventing lactate formation. Therefore, the aim of this study ...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.22003
更新日期:2012-12-01 00:00:00
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journal_title:Cancer biology & therapy
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doi:10.4161/cbt.7.4.5535
更新日期:2008-04-01 00:00:00
abstract::Non-small cell lung cancer (NSCLC) remains recalcitrant to effective treatment due to tumor relapse and acquired resistance. Cancer stem cells (CSCs) are believed to be one mechanism for relapse and resistance and are consequently considered promising drug targets. We report that chetomin, an active component of Chaet...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
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更新日期:2020-08-02 00:00:00
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journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.11.2.13798
更新日期:2011-01-15 00:00:00
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journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.4.12.2183
更新日期:2005-12-01 00:00:00
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journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.6.10.4725
更新日期:2007-10-01 00:00:00
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journal_title:Cancer biology & therapy
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更新日期:2008-01-01 00:00:00
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journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.1080/15384047.2020.1856756
更新日期:2021-01-02 00:00:00
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journal_title:Cancer biology & therapy
pub_type: 杂志文章
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更新日期:2019-01-01 00:00:00
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journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.7.11.6837
更新日期:2008-11-01 00:00:00
abstract::Colorectal cancer (CRC) is the second most prevalent and deadly cancer worldwide. Due to the mortality and morbidity associated with chemotherapeutic regimes, research is turning to natural product enhancement of the acute apoptotic response to genotoxic carcinogens (AARGC). Although Tyrian purple dye pigments and pre...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.9.5.10887
更新日期:2010-03-01 00:00:00
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journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.7.12.6966
更新日期:2008-12-01 00:00:00
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journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.1080/15384047.2019.1647054
更新日期:2019-01-01 00:00:00
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journal_title:Cancer biology & therapy
pub_type: 杂志文章,评审
doi:10.4161/cbt.22958
更新日期:2013-02-01 00:00:00
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journal_title:Cancer biology & therapy
pub_type: 杂志文章,评审
doi:10.4161/cbt.10.5.13022
更新日期:2010-09-01 00:00:00
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journal_title:Cancer biology & therapy
pub_type: 杂志文章,评审
doi:10.4161/cbt.5.7.2972
更新日期:2006-07-01 00:00:00
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journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.10.9.13238
更新日期:2010-11-01 00:00:00
abstract::Phosphoinositide-3-kinase regulatory subunit 3(PIK3R3) is overexpressed in different types of human cancer. We previously reported the important role of PIK3R3 in colorectal cancer (CRC). However, the prognosis effect of PIK3R3 in CRC is still remaining unclear. In this study, we explored online clinical databases to ...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.1080/15384047.2017.1416936
更新日期:2018-03-04 00:00:00
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journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.29183
更新日期:2014-08-01 00:00:00
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journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.8.5.7687
更新日期:2009-03-01 00:00:00
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journal_title:Cancer biology & therapy
pub_type: 杂志文章
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更新日期:2011-10-01 00:00:00
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journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.1.1.41
更新日期:2002-01-01 00:00:00
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journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.3.9.1040
更新日期:2004-09-01 00:00:00
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journal_title:Cancer biology & therapy
pub_type: 杂志文章,随机对照试验
doi:10.4161/cbt.8.9.8129
更新日期:2009-05-01 00:00:00
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journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/15384047.2014.972799
更新日期:2014-01-01 00:00:00
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journal_title:Cancer biology & therapy
pub_type: 杂志文章,评审
doi:10.4161/cbt.2.5.445
更新日期:2003-09-01 00:00:00
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journal_title:Cancer biology & therapy
pub_type: 杂志文章,多中心研究
doi:10.4161/cbt.8.21.9737
更新日期:2009-11-01 00:00:00
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journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.4.4.1622
更新日期:2005-04-01 00:00:00
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journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.8.3.7485
更新日期:2009-02-01 00:00:00
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journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.3.10.1113
更新日期:2004-10-01 00:00:00