Abstract:
:STAT3 has been strongly implicated in human malignancies, and constitutive activation of STAT3 serves a crucial role in cell survival, angiogenesis, immune evasion, and inflammation. In this study, we showed that nitidine chloride, a natural phytochemical alkaloid derived from Zanthoxylum nitidum (Roxb) DC, exerts potent anticancer activity through STAT3 signaling cascade. Nitidine chloride dose dependently suppressed VEGF-induced endothelial cell proliferation, migration, and tubular structure formation in vitro and dramatically reduced VEGF-triggered neovascularization in mouse cornea and Matrigel plugs in vivo. This angiogenesis inhibition mediated by nitidine chloride was well interpreted by the suppression of Janus kinase 2/STAT3 signaling and STAT3 DNA-binding activity in endothelial cells. Furthermore, nitidine chloride suppressed the constitutively activated STAT3 protein, its DNA-binding activity, and the expression of STAT3-dependent target genes, including cyclin D1, Bcl-xL, and VEGF in human gastric cancer cells. Consistent with the earlier findings, nitidine chloride inhibited gastric tumor cell growth and induced tumor cell apoptosis in vitro and effectively suppressed the volume, weight, and microvessel density of human SGC-7901 gastric solid tumors (n = 8) at a dosage of 7 mg/kg/d (intraperitoneal injection). Immunohistochemistry and Western blot analysis further revealed that the expression of STAT3, CD31, and VEGF protein in xenografts was remarkably decreased by the alkaloid. Taken together, we propose that nitidine chloride is a promising anticancer drug candidate as a potent STAT3 signaling inhibitor.
journal_name
Mol Cancer Therjournal_title
Molecular cancer therapeuticsauthors
Chen J,Wang J,Lin L,He L,Wu Y,Zhang L,Yi Z,Chen Y,Pang X,Liu Mdoi
10.1158/1535-7163.MCT-11-0648subject
Has Abstractpub_date
2012-02-01 00:00:00pages
277-87issue
2eissn
1535-7163issn
1538-8514pii
1535-7163.MCT-11-0648journal_volume
11pub_type
杂志文章abstract::Mithramycin A is a DNA-binding antitumor agent, which has been clinically used in the therapies of several types of cancer and Paget's disease. In this study, we investigated the combined effect of mithramycin A and tumor necrosis factor-alpha-related apoptosis-inducing ligand (TRAIL) on apoptosis of cancer cells. In ...
journal_title:Molecular cancer therapeutics
pub_type: 杂志文章
doi:10.1158/1535-7163.MCT-06-0426
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journal_title:Molecular cancer therapeutics
pub_type: 杂志文章
doi:10.1158/1535-7163.MCT-06-0580
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journal_title:Molecular cancer therapeutics
pub_type: 杂志文章
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journal_title:Molecular cancer therapeutics
pub_type: 杂志文章
doi:10.1158/1535-7163.MCT-13-0006-T
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journal_title:Molecular cancer therapeutics
pub_type: 杂志文章
doi:10.1158/1535-7163.MCT-18-0837
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journal_title:Molecular cancer therapeutics
pub_type: 杂志文章
doi:10.1158/1535-7163.MCT-08-0012
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pub_type: 杂志文章
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journal_title:Molecular cancer therapeutics
pub_type: 杂志文章
doi:
更新日期:2002-10-01 00:00:00
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journal_title:Molecular cancer therapeutics
pub_type: 杂志文章
doi:10.1158/1535-7163.MCT-05-0046
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pub_type: 杂志文章
doi:10.1158/1535-7163.MCT-09-0101
更新日期:2009-06-01 00:00:00
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journal_title:Molecular cancer therapeutics
pub_type: 杂志文章
doi:10.1158/1535-7163.MCT-08-0149
更新日期:2009-01-01 00:00:00
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journal_title:Molecular cancer therapeutics
pub_type: 杂志文章
doi:10.1158/1535-7163.MCT-14-1057
更新日期:2015-08-01 00:00:00
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journal_title:Molecular cancer therapeutics
pub_type: 杂志文章
doi:10.1158/1535-7163.MCT-11-0667
更新日期:2012-03-01 00:00:00
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journal_title:Molecular cancer therapeutics
pub_type: 杂志文章
doi:10.1158/1535-7163.MCT-13-0924
更新日期:2014-05-01 00:00:00
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pub_type: 杂志文章
doi:10.1158/1535-7163.MCT-17-0137
更新日期:2018-05-01 00:00:00
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journal_title:Molecular cancer therapeutics
pub_type: 杂志文章
doi:10.1158/1535-7163.MCT-19-0826
更新日期:2020-08-01 00:00:00
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journal_title:Molecular cancer therapeutics
pub_type: 杂志文章
doi:10.1158/1535-7163.MCT-16-0011
更新日期:2017-03-01 00:00:00
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journal_title:Molecular cancer therapeutics
pub_type: 杂志文章
doi:10.1158/1535-7163.MCT-08-0183
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-09-0906
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journal_title:Molecular cancer therapeutics
pub_type: 杂志文章
doi:10.1158/1535-7163.MCT-07-0180
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pub_type: 杂志文章
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journal_title:Molecular cancer therapeutics
pub_type: 杂志文章
doi:10.1158/1535-7163.MCT-17-0982
更新日期:2018-10-01 00:00:00
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journal_title:Molecular cancer therapeutics
pub_type: 杂志文章
doi:10.1158/1535-7163.MCT-06-0424
更新日期:2006-12-01 00:00:00
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journal_title:Molecular cancer therapeutics
pub_type: 杂志文章
doi:10.1158/1535-7163.MCT-18-0212
更新日期:2018-10-01 00:00:00
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journal_title:Molecular cancer therapeutics
pub_type:
doi:10.1158/1535-7163.MCT-09-0491
更新日期:2010-01-01 00:00:00
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journal_title:Molecular cancer therapeutics
pub_type: 杂志文章
doi:
更新日期:2002-05-01 00:00:00
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journal_title:Molecular cancer therapeutics
pub_type: 杂志文章
doi:10.1158/1535-7163.MCT-12-1218
更新日期:2013-10-01 00:00:00
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journal_title:Molecular cancer therapeutics
pub_type: 杂志文章
doi:10.1158/1535-7163.MCT-11-0152
更新日期:2011-08-01 00:00:00
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journal_title:Molecular cancer therapeutics
pub_type: 杂志文章
doi:10.1158/1535-7163.MCT-17-0442
更新日期:2018-01-01 00:00:00
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journal_title:Molecular cancer therapeutics
pub_type: 杂志文章
doi:10.1158/1535-7163.MCT-18-1045
更新日期:2019-06-01 00:00:00