Abstract:
:Dietary phytochemicals exhibit chemopreventive potential in vivo through persistent low-dose exposures, whereas mechanistic in vitro studies with these agents generally use a high-dose single treatment. Because the latter approach is not representative of an in vivo steady state, we investigated antitumor activity of curcumin, 3,3'-diindolylmethane (DIM), epigallocatechin gallate (EGCG), genistein, or indole-3-carbinol (I3C) in breast cancer MDA-MB-231 cells, exposed in long-term culture to low concentrations, achievable in vivo. Curcumin and EGCG increased cell doubling time. Curcumin, EGCG, and I3C inhibited clonogenic growth by 55% to 60% and induced 1.5- to 2-fold higher levels of the basal caspase-3/7 activity. No changes in expression of cell cycle-related proteins or survivin were found; however, I3C reduced epidermal growth factor receptor expression, contributing to apoptosis. Because some phytochemicals are shown to inhibit DNA and histone modification, modulation of expression by the agents in a set of genes (cadherin-11, p21Cip1, urokinase-type plasminogen activator, and interleukin-6) was compared with changes induced by inhibitors of DNA methylation or histone deacetylation. The phytochemicals modified protein and/or RNA expression of these genes, with EGCG eliciting the least and DIM the most changes in gene expression. DIM and curcumin decreased cadherin-11 and increased urokinase-type plasminogen activator levels correlated with increased cell motility. Curcumin, DIM, EGCG, and genistein reduced cell sensitivity to radiation-induced DNA damage without affecting DNA repair. This model has revealed that apoptosis and not arrest is likely to be responsible for growth inhibition. It also implicated new molecular targets and activities of the agents under conditions relevant to human exposure.
journal_name
Mol Cancer Therjournal_title
Molecular cancer therapeuticsauthors
Moiseeva EP,Almeida GM,Jones GD,Manson MMdoi
10.1158/1535-7163.MCT-07-0117subject
Has Abstractpub_date
2007-11-01 00:00:00pages
3071-9issue
11eissn
1535-7163issn
1538-8514pii
6/11/3071journal_volume
6pub_type
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journal_title:Molecular cancer therapeutics
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pub_type: 杂志文章
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pub_type: 杂志文章
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pub_type: 杂志文章,评审
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pub_type: 杂志文章
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更新日期:2020-08-01 00:00:00
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pub_type: 杂志文章,评审
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journal_title:Molecular cancer therapeutics
pub_type: 杂志文章
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更新日期:2008-06-01 00:00:00
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pub_type: 杂志文章
doi:10.1158/1535-7163.MCT-15-0577-T
更新日期:2016-05-01 00:00:00
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doi:10.1158/1535-7163.MCT-17-0342
更新日期:2017-11-01 00:00:00
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pub_type: 杂志文章
doi:10.1158/1535-7163.MCT-19-0776
更新日期:2020-07-01 00:00:00
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pub_type: 杂志文章
doi:10.1158/1535-7163.MCT-18-0770
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journal_title:Molecular cancer therapeutics
pub_type: 杂志文章
doi:10.1158/1535-7163.MCT-12-0798
更新日期:2013-05-01 00:00:00
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journal_title:Molecular cancer therapeutics
pub_type: 杂志文章
doi:10.1158/1535-7163.MCT-13-0966
更新日期:2014-06-01 00:00:00
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journal_title:Molecular cancer therapeutics
pub_type: 杂志文章
doi:10.1158/1535-7163.MCT-09-1009
更新日期:2010-06-01 00:00:00
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pub_type: 杂志文章
doi:10.1158/1535-7163.MCT-11-0534
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journal_title:Molecular cancer therapeutics
pub_type: 杂志文章
doi:10.1158/1535-7163.MCT-08-0051
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journal_title:Molecular cancer therapeutics
pub_type: 杂志文章
doi:10.1158/1535-7163.MCT-11-0161
更新日期:2011-07-01 00:00:00
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journal_title:Molecular cancer therapeutics
pub_type: 杂志文章
doi:10.1158/1535-7163.MCT-08-1179
更新日期:2009-10-01 00:00:00
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journal_title:Molecular cancer therapeutics
pub_type: 杂志文章
doi:
更新日期:2003-03-01 00:00:00
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journal_title:Molecular cancer therapeutics
pub_type: 杂志文章
doi:10.1158/1535-7163.MCT-08-0015
更新日期:2008-08-01 00:00:00
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journal_title:Molecular cancer therapeutics
pub_type: 杂志文章
doi:10.1158/1535-7163.MCT-06-0066
更新日期:2006-07-01 00:00:00
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journal_title:Molecular cancer therapeutics
pub_type: 杂志文章
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更新日期:2008-04-01 00:00:00
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journal_title:Molecular cancer therapeutics
pub_type: 杂志文章
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更新日期:2016-10-01 00:00:00
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journal_title:Molecular cancer therapeutics
pub_type: 杂志文章
doi:10.1158/1535-7163.MCT-15-0982
更新日期:2016-06-01 00:00:00
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pub_type: 杂志文章
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更新日期:2015-02-01 00:00:00