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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
4
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pubmed:dateCreated |
2003-5-27
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pubmed:abstractText |
We previously reported synergistic induction of apoptosis by IFN-gamma plus either cyclosporin A (CsA) or tacrolimus (FK506) in gastric carcinoma cells. In this study, we aimed to elucidate the mechanism for this synergistic induction of apoptosis. IFN-gamma plus CsA synergistically induced caspase-3 mediated apoptosis in gastric carcinoma cells. Although IFN-gamma induced activation of signal transducer and activator of transcription1 (STAT1) and expression of interferon regulatory factor-1 (IRF-1) mRNA, IFN-gamma alone was not able to induce caspase-3 activation and apoptosis. When gastric carcinoma cells were treated with cyclohexamide, a protein synthesis inhibitor, following IFN-gamma pretreatment, caspase-3 was activated, and apoptosis was markedly induced. These findings suggest the existence of IFN-gamma-induced anti-apoptotic pathway and we evaluated the effect of IFN-gamma and CsA on calcium-sensitive nuclear factor-kappa B (NF-kappa B) activation. IFN-gamma increased intracellular calcium ion concentration ([Ca(2+)](i)) consisting of a spike and a sustained phase, and the latter was completely abrogated by CsA. Activation of NF-kappa B occurred in response to IFN-gamma, and which was markedly inhibited by either CsA or FK506. NF-kappa B decoy also enhanced the cytotoxic effect of IFN-gamma. These results suggest that IFN-gamma may simultaneously induce the STAT1-mediated apoptotic pathway and the anti-apoptotic pathway through calcium-activated NF-kappa B and that inhibition of the latter by CsA may result in dominance of the apoptosis-inducing pathway.
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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/Antineoplastic Agents,
http://linkedlifedata.com/resource/pubmed/chemical/CASP3 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Calcium,
http://linkedlifedata.com/resource/pubmed/chemical/Caspase 3,
http://linkedlifedata.com/resource/pubmed/chemical/Caspases,
http://linkedlifedata.com/resource/pubmed/chemical/Cycloheximide,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclosporine,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/IRF1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Interferon Regulatory Factor-1,
http://linkedlifedata.com/resource/pubmed/chemical/Interferon-gamma,
http://linkedlifedata.com/resource/pubmed/chemical/NF-kappa B,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphoproteins,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Synthesis Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/STAT1 Transcription Factor,
http://linkedlifedata.com/resource/pubmed/chemical/STAT1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Tacrolimus,
http://linkedlifedata.com/resource/pubmed/chemical/Trans-Activators
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pubmed:status |
MEDLINE
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pubmed:month |
Jun
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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 |
13
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pubmed:volume |
305
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
797-805
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pubmed:dateRevised |
2008-11-21
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pubmed:meshHeading |
pubmed-meshheading:12767900-Antineoplastic Agents,
pubmed-meshheading:12767900-Apoptosis,
pubmed-meshheading:12767900-Calcium,
pubmed-meshheading:12767900-Carcinoma,
pubmed-meshheading:12767900-Caspase 3,
pubmed-meshheading:12767900-Caspases,
pubmed-meshheading:12767900-Cycloheximide,
pubmed-meshheading:12767900-Cyclosporine,
pubmed-meshheading:12767900-DNA-Binding Proteins,
pubmed-meshheading:12767900-Drug Synergism,
pubmed-meshheading:12767900-Humans,
pubmed-meshheading:12767900-Interferon Regulatory Factor-1,
pubmed-meshheading:12767900-Interferon-gamma,
pubmed-meshheading:12767900-Models, Biological,
pubmed-meshheading:12767900-NF-kappa B,
pubmed-meshheading:12767900-Phosphoproteins,
pubmed-meshheading:12767900-Protein Synthesis Inhibitors,
pubmed-meshheading:12767900-RNA, Messenger,
pubmed-meshheading:12767900-STAT1 Transcription Factor,
pubmed-meshheading:12767900-Stomach Neoplasms,
pubmed-meshheading:12767900-Tacrolimus,
pubmed-meshheading:12767900-Trans-Activators,
pubmed-meshheading:12767900-Tumor Cells, Cultured
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pubmed:year |
2003
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pubmed:articleTitle |
Inhibition of interferon-gamma-activated nuclear factor-kappa B by cyclosporin A: A possible mechanism for synergistic induction of apoptosis by interferon-gamma and cyclosporin A in gastric carcinoma cells.
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pubmed:affiliation |
Department of Cancer Therapy and Research, Graduate School of Medical Sciences, Kyusyu University, Fukuoka 812-8582, Japan.
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pubmed:publicationType |
Journal Article
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