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HDAC4 degradation by combined TRAIL and valproic acid treatment induces apoptotic cell death of TRAIL-resistant head and neck cancer cellsoa mark
  • Lee, Bok Soon ;
  • Kim, Yeon Soo ;
  • Kim, Haeng Jun ;
  • Kim, Dae Ho ;
  • Won, Ho Ryun ;
  • Kim, Yong Sung ;
  • Kim, Chul Ho
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Publication Year
2018-12-01
Journal
Scientific Reports
Publisher
Nature Publishing Group
Citation
Scientific Reports, Vol.8 No.1
Mesh Keyword
CaspasesCell Line, TumorCell ProliferationCell SurvivalDrug Resistance, NeoplasmDrug SynergismGene Expression Regulation, NeoplasticGene Knockdown TechniquesHead and Neck NeoplasmsHistone DeacetylasesHumansProteolysisRepressor ProteinsSignal TransductionTNF-Related Apoptosis-Inducing LigandUp-RegulationValproic Acid
All Science Classification Codes (ASJC)
Multidisciplinary
Abstract
Although TRAIL can directly induce cell death in some cancer cells, it appears that TRAIL resistance exists in many cancers. This study focuses on anti-cancer drugs for TRAIL-resistant head and neck cancer (HNC) to provide further progress toward effective cancer therapy. Results indicate in TRAIL-resistant HNC cells, that combined TRAIL and VPA treatment greatly reduced cell viability and therefore induced cell death, relative to treatment with TRAIL or VPA alone. A caspase-dependent signaling pathway was demonstrated, and combined treatment with TRAIL and VPA also significantly decreased the expression of HDAC4. When we pretreated cells with z-VAD followed by combined treatment with TRAIL and VPA, cell death was blocked with no reduction in expression of HDAC4. To confirm that cell death involved HDAC4 in HNC cells, we knocked down expression of HDAC4 with siRNA, followed by treatment with TRAIL and VPA. Results showed that loss of HDAC4 sensitized the TRAIL-resistant HNC cells to apoptotic cell death. Finally, we showed elevated expression of HDAC4 in HNC tissues compared to normal tissues obtained from the same patients. In conclusion, we suggest that combined VPA and TRAIL treatment may be a promising therapy for HNC via HDAC4 degradation.
ISSN
2045-2322
Language
eng
URI
https://aurora.ajou.ac.kr/handle/2018.oak/30328
https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85051851840&origin=inward
DOI
https://doi.org/2-s2.0-85051851840
Journal URL
www.nature.com/srep/index.html
Type
Article
Funding
This work was supported by National Research Foundation of Korea grants funded by the Korea government (MSIP) (No. 2011-0030043:SRC to CH Kim, 2017M3A9F7079339 to CH Kim, 2018R1A2B3009008 to CH Kim and 2017R1D1A1B03028527 to BS Lee).
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