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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
2
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pubmed:dateCreated |
2002-8-1
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pubmed:abstractText |
Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is a type II transmembrane cytokine and a potent inducer of apoptosis. Epidermal growth factor (EGF) signaling is well known to involve in tumor survival and overexpression of EGF receptor (EGF-R) attributes to decreased responsiveness to many available therapies in cancer treatment. We investigated whether EGF-R inhibitors enhance TRAIL-induced apoptosis. We exposed A549 cells to Genistein, PD153035, and PD158780 for 12h and then treated with recombinant TRAIL protein. TRAIL alone induced 25% cell death after a 3-h treatment, but in cells pretreated with EGF-R inhibitors, TRAIL induced cell death to more than 70% after 3h treatment. Genistein enhanced TRAIL-induced apoptosis in a time- and dose-dependent manner. Western blot analyses showed that pretreatment with Genistein down-regulated the protein levels of total Akt and phosphorylated active Akt. Genistein also decreased the protein level of Bcl-XL that is regulated by Akt. These molecules are well characterized to act against induction of apoptotic cell death. Therefore, our data suggest that EGF-R inhibitor may sensitize A549 cells to TRAIL-induced apoptosis by regulating expression of these proteins. EGF-R inhibitors may play an important role in the anti-cancer activity of TRAIL protein, especially in TRAIL-resistant tumors that arise by expressing constitutively active Akt.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/4-((3-bromophenyl)amino)-6,7-dimetho...,
http://linkedlifedata.com/resource/pubmed/chemical/6-(methylamino)pyrido(3,4-d)pyrimidi...,
http://linkedlifedata.com/resource/pubmed/chemical/Apoptosis Regulatory Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Genistein,
http://linkedlifedata.com/resource/pubmed/chemical/Membrane Glycoproteins,
http://linkedlifedata.com/resource/pubmed/chemical/Protein-Serine-Threonine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-akt,
http://linkedlifedata.com/resource/pubmed/chemical/Pyrimidines,
http://linkedlifedata.com/resource/pubmed/chemical/Quinazolines,
http://linkedlifedata.com/resource/pubmed/chemical/Receptor, Epidermal Growth Factor,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/TNF-Related Apoptosis-Inducing...,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Necrosis Factor-alpha
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pubmed:status |
MEDLINE
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pubmed:month |
Jul
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pubmed:issn |
0006-291X
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
12
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pubmed:volume |
295
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
515-8
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:12150980-Apoptosis,
pubmed-meshheading:12150980-Apoptosis Regulatory Proteins,
pubmed-meshheading:12150980-Cell Line,
pubmed-meshheading:12150980-Genistein,
pubmed-meshheading:12150980-Membrane Glycoproteins,
pubmed-meshheading:12150980-Phosphorylation,
pubmed-meshheading:12150980-Protein-Serine-Threonine Kinases,
pubmed-meshheading:12150980-Proto-Oncogene Proteins,
pubmed-meshheading:12150980-Proto-Oncogene Proteins c-akt,
pubmed-meshheading:12150980-Pyrimidines,
pubmed-meshheading:12150980-Quinazolines,
pubmed-meshheading:12150980-Receptor, Epidermal Growth Factor,
pubmed-meshheading:12150980-Recombinant Proteins,
pubmed-meshheading:12150980-TNF-Related Apoptosis-Inducing Ligand,
pubmed-meshheading:12150980-Tumor Necrosis Factor-alpha
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pubmed:year |
2002
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pubmed:articleTitle |
Regulation of Akt by EGF-R inhibitors, a possible mechanism of EGF-R inhibitor-enhanced TRAIL-induced apoptosis.
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pubmed:affiliation |
Department of Surgery, University of Pittsburgh School of Medicine, BST W1513, Pittsburgh, PA 15261, USA.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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