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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
49
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pubmed:dateCreated |
2005-12-5
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pubmed:abstractText |
Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has been shown to be selective in the induction of apoptosis in cancer cells with minimal toxicity to normal tissues. However, not all cancers are sensitive to TRAIL-mediated apoptosis. Thus, TRAIL-resistant cancer cells must be sensitized first to become responsive to TRAIL. In this study, we observed that pretreatment by acetylsalicylic acid (ASA) augmented TRAIL-induced apoptotic death in human prostate adenocarcinoma LNCaP and human colorectal carcinoma CX-1 cells. Western blot analysis showed that pretreatment of ASA followed by TRAIL treatment activated caspases (8, 9, and 3) and cleaved poly(ADP-ribose) polymerase, the hallmark feature of apoptosis. Most interestingly, at least 12 h of pretreatment with ASA was prerequisite for promoting TRAIL-induced apoptosis and was related to down-regulation of BCL-2. Biochemical analysis revealed that ASA inhibited NF-kappaB activity, which is known to regulate BCL-2 gene expression, by dephosphorylating IkappaB-alpha and inhibiting IKKbeta activity but not by affecting the HER-2/neu phosphatidylinositol 3-kinase-Akt signal pathway. Overexpression of BCL-2 suppressed the promotive effect of ASA on TRAIL-induced apoptosis and changes in mitochondrial membrane potential. Taken together, our studies suggested that ASA-promoted TRAIL cytotoxicity is mediated through down-regulating BCL-2 and by decreasing mitochondrial membrane potential.
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pubmed:grant |
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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/Apoptosis Regulatory Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Aspirin,
http://linkedlifedata.com/resource/pubmed/chemical/CASP3 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/CASP8 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/CASP9 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Caspase 3,
http://linkedlifedata.com/resource/pubmed/chemical/Caspase 8,
http://linkedlifedata.com/resource/pubmed/chemical/Caspase 9,
http://linkedlifedata.com/resource/pubmed/chemical/Caspases,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/I-kappa B Kinase,
http://linkedlifedata.com/resource/pubmed/chemical/I-kappa B Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Membrane Glycoproteins,
http://linkedlifedata.com/resource/pubmed/chemical/NF-kappa B,
http://linkedlifedata.com/resource/pubmed/chemical/NF-kappaB inhibitor alpha,
http://linkedlifedata.com/resource/pubmed/chemical/Poly(ADP-ribose) Polymerases,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/TNF-Related Apoptosis-Inducing...,
http://linkedlifedata.com/resource/pubmed/chemical/TNFSF10 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Necrosis Factor-alpha
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pubmed:status |
MEDLINE
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pubmed:month |
Dec
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pubmed:issn |
0021-9258
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
9
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pubmed:volume |
280
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
41047-56
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:16199534-Apoptosis,
pubmed-meshheading:16199534-Apoptosis Regulatory Proteins,
pubmed-meshheading:16199534-Aspirin,
pubmed-meshheading:16199534-Blotting, Western,
pubmed-meshheading:16199534-Caspase 3,
pubmed-meshheading:16199534-Caspase 8,
pubmed-meshheading:16199534-Caspase 9,
pubmed-meshheading:16199534-Caspases,
pubmed-meshheading:16199534-Cell Line, Tumor,
pubmed-meshheading:16199534-Colonic Neoplasms,
pubmed-meshheading:16199534-Electrophoretic Mobility Shift Assay,
pubmed-meshheading:16199534-Enzyme Activation,
pubmed-meshheading:16199534-Enzyme Inhibitors,
pubmed-meshheading:16199534-Flow Cytometry,
pubmed-meshheading:16199534-Gene Expression Regulation,
pubmed-meshheading:16199534-Genes, bcl-2,
pubmed-meshheading:16199534-Humans,
pubmed-meshheading:16199534-I-kappa B Kinase,
pubmed-meshheading:16199534-I-kappa B Proteins,
pubmed-meshheading:16199534-In Situ Nick-End Labeling,
pubmed-meshheading:16199534-Male,
pubmed-meshheading:16199534-Membrane Glycoproteins,
pubmed-meshheading:16199534-Membrane Potentials,
pubmed-meshheading:16199534-Mitochondria,
pubmed-meshheading:16199534-NF-kappa B,
pubmed-meshheading:16199534-Phosphorylation,
pubmed-meshheading:16199534-Poly(ADP-ribose) Polymerases,
pubmed-meshheading:16199534-Prostatic Neoplasms,
pubmed-meshheading:16199534-Recombinant Proteins,
pubmed-meshheading:16199534-Reverse Transcriptase Polymerase Chain Reaction,
pubmed-meshheading:16199534-TNF-Related Apoptosis-Inducing Ligand,
pubmed-meshheading:16199534-Transfection,
pubmed-meshheading:16199534-Tumor Necrosis Factor-alpha
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pubmed:year |
2005
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pubmed:articleTitle |
Pretreatment of acetylsalicylic acid promotes tumor necrosis factor-related apoptosis-inducing ligand-induced apoptosis by down-regulating BCL-2 gene expression.
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pubmed:affiliation |
Department of Surgery and Pharmacology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15213, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, Non-P.H.S.,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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