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Phytosphingosine in combination with TRAIL sensitizes cancer cells to TRAIL through synergistic up-regulation of DR4 and DR5.

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dc.contributor.authorChoi, SY-
dc.contributor.authorKim, MJ-
dc.contributor.authorChung, HY-
dc.contributor.authorLee, SJ-
dc.contributor.authorJang, YJ-
dc.date.accessioned2011-03-16T04:50:09Z-
dc.date.available2011-03-16T04:50:09Z-
dc.date.issued2007-
dc.identifier.issn1021-335X-
dc.identifier.urihttp://repository.ajou.ac.kr/handle/201003/1737-
dc.description.abstractSensitization of cancer cells to TRAIL could improve the effectiveness of TRAIL as an anticancer agent. We explored whether TRAIL in combination with phytosphingosine could sensitize cancer cells to TRAIL. The combined treatment enhanced synergistic apoptotic cell death of Jurkat T cells, compared to TRAIL or phytosphingosine alone. Enhanced apoptosis in response to the combination treatment was associated with caspase-8 activation-mediated Bax and Bak activation and mitochondrial dysfunction. The combination treatment also resulted in synergistic up-regulation of TRAIL receptor R1 (DR4) and R2 (DR5). siRNA targeting of DR5 significantly attenuated the combination treatment-induced caspase-8 activation, mitochondrial dysfunction, and apoptotic cell death. Upon stimulation of cells with the combination treatment, NF-kappaB was activated. Moreover, siRNA targeting of NF-kappaB significantly attenuated the combination treatment-induced DR4 and DR5 expression and receptor-mediated caspase-8 activation. These results indicate that phytosphingosine sensitizes cancer cells to TRAIL through the synergistic up-regulation of DR4 and DR5 in an NF-kappaB-dependent fashion resulting in caspase-8 activation and subsequent mitochondrial dysfunction. These findings support the potential application of combination treatment with TRAIL and phytosphingosine in the treatment of cancers that are less sensitive to TRAIL.-
dc.language.isoen-
dc.subject.MESHAntineoplastic Combined Chemotherapy Protocols-
dc.subject.MESHApoptosis-
dc.subject.MESHBH3 Interacting Domain Death Agonist Protein-
dc.subject.MESHCarcinoma, Non-Small-Cell Lung-
dc.subject.MESHCaspase 8-
dc.subject.MESHDrug Synergism-
dc.subject.MESHEnzyme Activation-
dc.subject.MESHHumans-
dc.subject.MESHJurkat Cells-
dc.subject.MESHLung Neoplasms-
dc.subject.MESHLymphoma, T-Cell-
dc.subject.MESHMitochondria-
dc.subject.MESHNF-kappa B-
dc.subject.MESHReceptors, TNF-Related Apoptosis-Inducing Ligand-
dc.subject.MESHReceptors, Tumor Necrosis Factor-
dc.subject.MESHRecombinant Proteins-
dc.subject.MESHSphingosine-
dc.subject.MESHT-Lymphocytes-
dc.subject.MESHTNF-Related Apoptosis-Inducing Ligand-
dc.subject.MESHUp-Regulation-
dc.subject.MESHbcl-2 Homologous Antagonist-Killer Protein-
dc.subject.MESHbcl-2-Associated X Protein-
dc.titlePhytosphingosine in combination with TRAIL sensitizes cancer cells to TRAIL through synergistic up-regulation of DR4 and DR5.-
dc.typeArticle-
dc.identifier.pmid17143496-
dc.identifier.urlhttp://www.spandidos-publications.com/or/17/1/175-
dc.contributor.affiliatedAuthor장, 영주-
dc.type.localJournal Papers-
dc.citation.titleOncology reports-
dc.citation.volume17-
dc.citation.number1-
dc.citation.date2007-
dc.citation.startPage175-
dc.citation.endPage184-
dc.identifier.bibliographicCitationOncology reports, 17(1). : 175-184, 2007-
dc.identifier.eissn1791-2431-
dc.relation.journalidJ01021335X-
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Journal Papers > School of Medicine / Graduate School of Medicine > Microbiology
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