Source:http://linkedlifedata.com/resource/pubmed/id/19885602
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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
6
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pubmed:dateCreated |
2009-11-3
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pubmed:abstractText |
Secreted Wingless type (Wnt) ligands have previously been shown to be involved in tumor developmental processes and oncogenesis. Aberrant promoter methylation of Wnt inhibitory factor-1 (WIF-1) is a fundamental mechanism of epigenetic silencing in human cancers. Procaine, a local anesthetic drug, and procainamide, a drug for the treatment of cardiac arrhythmias, have been reported as inhibitors of DNA methylation, causing demethylation and reactivation of methylation-silenced genes such as RARbeta and GSTP1. The promoter demethylation of WIF-1 has not previously been reported on. We demonstrated previously that WIF-1 is silenced due to promoter hypermethylation in lung cancer cell lines. In this study, we demonstrate promoter demethylation of WIF-1; restoration of WIF-1 expression, and underexpression of cytosolic beta-catenin protein and TCF reporter activity, after procaine and procainamide treatment in H460 and A549 cell lines. Our results provide the first evidence that procaine and procainamide reactivate WIF-1 in these cancer cells and downregulate the Wnt canonical pathway. These results further suggest that procaine and procainamide may have a potential use for preventing the development of lung cancer.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Adaptor Proteins, Signal Transducing,
http://linkedlifedata.com/resource/pubmed/chemical/Anesthetics, Local,
http://linkedlifedata.com/resource/pubmed/chemical/Anti-Arrhythmia Agents,
http://linkedlifedata.com/resource/pubmed/chemical/Procainamide,
http://linkedlifedata.com/resource/pubmed/chemical/Procaine,
http://linkedlifedata.com/resource/pubmed/chemical/Repressor Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/WIF1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Wnt Proteins
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pubmed:status |
MEDLINE
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pubmed:month |
Dec
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pubmed:issn |
1791-2431
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pubmed:author | |
pubmed:issnType |
Electronic
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pubmed:volume |
22
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1479-84
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pubmed:meshHeading |
pubmed-meshheading:19885602-Adaptor Proteins, Signal Transducing,
pubmed-meshheading:19885602-Anesthetics, Local,
pubmed-meshheading:19885602-Anti-Arrhythmia Agents,
pubmed-meshheading:19885602-Cell Line, Tumor,
pubmed-meshheading:19885602-Cell Proliferation,
pubmed-meshheading:19885602-DNA Methylation,
pubmed-meshheading:19885602-Dose-Response Relationship, Drug,
pubmed-meshheading:19885602-Gene Expression Regulation, Neoplastic,
pubmed-meshheading:19885602-Gene Silencing,
pubmed-meshheading:19885602-Humans,
pubmed-meshheading:19885602-Lung Neoplasms,
pubmed-meshheading:19885602-Procainamide,
pubmed-meshheading:19885602-Procaine,
pubmed-meshheading:19885602-Promoter Regions, Genetic,
pubmed-meshheading:19885602-Repressor Proteins,
pubmed-meshheading:19885602-Wnt Proteins
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pubmed:year |
2009
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pubmed:articleTitle |
Procaine and procainamide inhibit the Wnt canonical pathway by promoter demethylation of WIF-1 in lung cancer cells.
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pubmed:affiliation |
Department of Cardiothoracic Surgery, Beijing Friendship Hospital, Capital Medical University, Beijing, PR China.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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