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Capsaicin sensitizes malignant glioma cells to TRAIL-mediated apoptosis via DR5 upregulation and survivin downregulation.

DC Field Value Language
dc.contributor.authorKim, JY-
dc.contributor.authorKim, EH-
dc.contributor.authorKim, SU-
dc.contributor.authorKwon, TK-
dc.contributor.authorChoi, KS-
dc.date.accessioned2011-05-31T01:46:50Z-
dc.date.available2011-05-31T01:46:50Z-
dc.date.issued2010-
dc.identifier.issn0143-3334-
dc.identifier.urihttp://repository.ajou.ac.kr/handle/201003/2728-
dc.description.abstractCapsaicin, a pungent ingredient of red chili peppers, has been reported to possess antitumor activities. Here, we show that subtoxic doses of capsaicin effectively sensitize multiple malignant glioma cell lines to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis. Although TRAIL alone mediated partial proteolytic processing of procaspase-3 in glioma cells, cotreatment with capsaicin and TRAIL efficiently restored complete activation of caspases. We found that treatment of various gliomas with capsaicin significantly upregulated DR5, a death receptor of TRAIL, and downregulated the caspase inhibitor survivin. The induction of DR5 was mediated by CHOP/GADD153. The reduction in survivin protein level was associated with downregulation of cyclin B and Cdc2 expression, suggesting that inhibition of Cdc2 activity might contribute to capsaicin-induced survivin downregulation. Taken together, these results indicate that the activity of capsaicin toward DR5 and survivin contributes to the amplification of caspase cascades, thereby restoring TRAIL sensitivity in malignant glioma cells. Interestingly, normal astrocytes were resistant to combined treatment with capsaicin and TRAIL. Neither capsaicin-induced DR5 upregulation/survivin downregulation nor the partial processing of procaspase-3 by TRAIL was induced in astrocytes. Thus, a combined regimen using capsaicin and TRAIL may provide a safe and effective strategy for treating malignant gliomas.-
dc.language.isoen-
dc.subject.MESHApoptosis-
dc.subject.MESHAstrocytes-
dc.subject.MESHCapsaicin-
dc.subject.MESHCaspases-
dc.subject.MESHCell Line, Tumor-
dc.subject.MESHCells, Cultured-
dc.subject.MESHCyclin B-
dc.subject.MESHDown-Regulation-
dc.subject.MESHGlioma-
dc.subject.MESHHumans-
dc.subject.MESHMicrotubule-Associated Proteins-
dc.subject.MESHNeoplasm Proteins-
dc.subject.MESHRNA, Small Interfering-
dc.subject.MESHReceptors, TNF-Related Apoptosis-Inducing Ligand-
dc.subject.MESHRecombinant Fusion Proteins-
dc.subject.MESHRecombinant Proteins-
dc.subject.MESHSignal Transduction-
dc.subject.MESHTNF-Related Apoptosis-Inducing Ligand-
dc.subject.MESHTranscription Factor CHOP-
dc.subject.MESHUp-Regulation-
dc.titleCapsaicin sensitizes malignant glioma cells to TRAIL-mediated apoptosis via DR5 upregulation and survivin downregulation.-
dc.typeArticle-
dc.identifier.pmid19939880-
dc.identifier.urlhttp://carcin.oxfordjournals.org/cgi/pmidlookup?view=long&pmid=19939880-
dc.contributor.affiliatedAuthor최, 경숙-
dc.type.localJournal Papers-
dc.identifier.doi10.1093/carcin/bgp298-
dc.citation.titleCarcinogenesis-
dc.citation.volume31-
dc.citation.number3-
dc.citation.date2010-
dc.citation.startPage367-
dc.citation.endPage375-
dc.identifier.bibliographicCitationCarcinogenesis, 31(3). : 367-375, 2010-
dc.identifier.eissn1460-2180-
dc.relation.journalidJ001433334-
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Biochemistry & Molecular Biology
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