Abstract:
:The peptidyl prolyl isomerase (Pin1) that induces cis-trans isomerization of the peptide bond involving serine/threonine-proline has recently been shown to regulate the activity of many phosphoproteins including the ones involved in damage response pathways. We investigated Pin1 as a potential target for enhancing the efficacy of anticancer therapy by studying the effects of juglone, a Pin1 inhibitor on the cytotoxicity of etoposide (a widely used anticancer drug that targets topoisomerase IIα) in human tumor cell lines. Treatment of cells with juglone synergistically enhanced the cytotoxicity of etoposide (loss of clonogenicity) with a tenfold increase when etoposide treatment preceded juglone exposure. On the other hand, the toxicity was than additive when the treatment protocol was reversed (i.e exposure to juglone followed by etoposide treatment). This suggests that Pin1 inhibition possibly reduces the induction of initial DNA damage by etoposide, which was supported by a decrease in the levels of chromatin bound topoIIα. Increase in the etoposide induced toxicity by juglone appeared to be mainly due to enhanced mitotic cell death linked to cytogenetic damage, although a moderate increase in interphase (apoptotic) death was also evident as revealed by DNA degradation (hypodiploid population and TUNEL assay). Since the level of Pin1 is found to be higher in cancer cells, this enzyme could be a potential target for developing an adjuvant to enhance the efficacy of anticancer therapies.
journal_name
Curr Cancer Drug Targetsjournal_title
Current cancer drug targetsauthors
Mathur R,Chandna S,N Kapoor P,S Dwarakanath Bdoi
10.2174/156800911794519761subject
Has Abstractpub_date
2011-03-01 00:00:00pages
380-92issue
3eissn
1568-0096issn
1873-5576pii
EPub-Abstract-CCDT-114journal_volume
11pub_type
杂志文章abstract::Heat shock proteins (HSPs) are molecular chaperones that stabilize folding and conformation of normal as well as oncogenic proteins. These chaperones thereby prevent the formation of protein aggregates. HSPs are often overexpressed in human malignancies, including AML. HSP90 is the main chaperon required for the stabi...
journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
doi:10.2174/156800909789271486
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journal_title:Current cancer drug targets
pub_type: 杂志文章
doi:10.2174/1568009620666200703152523
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journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
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journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
doi:10.2174/156800909787314002
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abstract::Angiogenesis is crucial for tumor development and progression, and antiangiogenetic therapy represents a promising approach for cancer treatment. Thus, the in-depth understanding of the molecular mechanism(s) regulating angiogenesis, together with the characterization of molecules expressed by endothelial cells and in...
journal_title:Current cancer drug targets
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journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
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journal_title:Current cancer drug targets
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journal_title:Current cancer drug targets
pub_type: 杂志文章
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更新日期:2011-06-01 00:00:00
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journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
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journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
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journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
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更新日期:2004-06-01 00:00:00
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journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
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更新日期:2005-06-01 00:00:00
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journal_title:Current cancer drug targets
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更新日期:2012-09-01 00:00:00
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journal_title:Current cancer drug targets
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journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
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journal_title:Current cancer drug targets
pub_type: 杂志文章
doi:10.2174/1568009620666200424145622
更新日期:2020-01-01 00:00:00
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journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
doi:10.2174/156800910793358041
更新日期:2010-12-01 00:00:00
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journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
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更新日期:2012-02-01 00:00:00
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journal_title:Current cancer drug targets
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doi:10.2174/1568009615666150506093155
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journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
doi:10.2174/1568009616666160922102641
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journal_title:Current cancer drug targets
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journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
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journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
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更新日期:2007-03-01 00:00:00
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journal_title:Current cancer drug targets
pub_type: 杂志文章
doi:10.2174/1568009618666180629150927
更新日期:2019-01-01 00:00:00
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journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
doi:10.2174/156800911796798968
更新日期:2011-09-01 00:00:00
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journal_title:Current cancer drug targets
pub_type: 杂志文章
doi:10.2174/156800909789057024
更新日期:2009-08-01 00:00:00
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journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
doi:10.2174/1568009620666200115160805
更新日期:2020-01-01 00:00:00
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journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
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更新日期:2016-01-01 00:00:00
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journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
doi:10.2174/1568009616666160216130608
更新日期:2017-01-01 00:00:00
abstract::Arsenic trioxide (As2O3) has been used in the clinic for the treatment of acute promyelocytic 1eukemia and some solid tumors. However, its effectiveness against lung cancer has not been well demonstrated, and the underlying mechanism(s) of action remain unclear. In the present study, we found that As2O3 significantly ...
journal_title:Current cancer drug targets
pub_type: 杂志文章
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更新日期:2014-01-01 00:00:00