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Valproic Acid Sensitizes TRAIL-Resistant Anaplastic Thyroid Carcinoma Cells to Apoptotic Cell Death.

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dc.contributor.authorCha, HY-
dc.contributor.authorLee, BS-
dc.contributor.authorKang, S-
dc.contributor.authorShin, YS-
dc.contributor.authorChang, JW-
dc.contributor.authorSung, ES-
dc.contributor.authorKim, YS-
dc.contributor.authorChoi, JW-
dc.contributor.authorKim, JH-
dc.contributor.authorKim, CH-
dc.date.accessioned2014-05-29T02:49:37Z-
dc.date.available2014-05-29T02:49:37Z-
dc.date.issued2013-
dc.identifier.issn1068-9265-
dc.identifier.urihttp://repository.ajou.ac.kr/handle/201003/10273-
dc.description.abstractBACKGROUND: Anaplastic thyroid carcinoma (ATC) is an aggressive human tumor associated with a median survival of 2-6 months. TRAIL, as a ligand of death receptors, is known to induce apoptotic cell death in several cancer cells. However, TRAIL treatment alone is not effective against TRAIL-resistant cancer cells. This study was designed to investigate whether valproic acid (VPA) enhances apoptotic cell death of TRAIL-resistant ATC cells and to identify the mechanism of cell death of ATC cells by combination treatment with VPA and TRAIL.



METHODS: To evaluate the cytotoxic effect of TRAIL and/or VPA on ATC cells, we used the MTT assay. The effects of VPA and TRAIL on apoptosis were assessed using FACS analysis (Annexin-V/PI stain) and Western blotting.



RESULTS: The combination of VPA with TRAIL significantly induced apoptotic cell death compared with 8505C and ARO cells treated with TRAIL alone. The protein levels of cleaved caspase-8, -3, and PARP were increased in VPA and TRAIL co-treated ARO cells. The combination induced the activation of JNK and the phosphorylation of FADD and c-Jun but not p38. However, pretreatment with caspase inhibitors reduced the expression of cleaved caspase-8, -3, and PARP in co-treated ARO cells. SP600125 remarkably reduced the expression of cleaved caspase-8, -3, and PARP and the phosphorylation of FADD and c-Jun, as well as apoptotic cell death.



CONCLUSIONS: VPA sensitized TRAIL-resistant ATC cells to apoptotic cell death through involvement of the JNK pathway. Thus, the combination of VPA and TRAIL may be a promising therapy for ATC.
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dc.language.isoen-
dc.titleValproic Acid Sensitizes TRAIL-Resistant Anaplastic Thyroid Carcinoma Cells to Apoptotic Cell Death.-
dc.typeArticle-
dc.identifier.pmid23982257-
dc.contributor.affiliatedAuthor이, 복순-
dc.contributor.affiliatedAuthor신, 유섭-
dc.contributor.affiliatedAuthor장, 재원-
dc.contributor.affiliatedAuthor김, 장희-
dc.contributor.affiliatedAuthor김, 철호-
dc.type.localJournal Papers-
dc.identifier.doi10.1245/s10434-013-3232-y-
dc.citation.titleAnnals of surgical oncology-
dc.citation.volume20 Suppl 3-
dc.citation.date2013-
dc.citation.startPage716-
dc.citation.endPage724-
dc.identifier.bibliographicCitationAnnals of surgical oncology, 20 Suppl 3. : 716-724, 2013-
dc.identifier.eissn1534-4681-
dc.relation.journalidJ010689265-
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Otolaryngology
Journal Papers > School of Medicine / Graduate School of Medicine > Pathology
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