The combination of silencing BAG3 and inhibition of the JNK pathway enhances hyperthermia sensitivity in human oral squamous cell carcinoma cells

Tatsuya Yunoki*, Ayako Kariya, Takashi Kondo, Atsushi Hayashi, Yoshiaki Tabuchi

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

23 Scopus citations

Abstract

Hyperthermia (HT) is a widely used physical treatment for various cancers, but its effect is often insufficient because of cytoprotective effects of heat shock proteins. BAG3, a co-chaperone of the heat shock protein 70, is a stress-inducible protein and demonstrates a cytoprotective property against various stresses, including heat stress. Here, we examined the effects of silencing the BAG3 on the sensitivity to HT in human oral squamous cell carcinoma (OSCC) HSC-3 cells. HT (44. °C, 90. min) was significantly increased in apoptotic cells concomitant with the activations of caspase-3 and c-Jun N-terminal kinase (JNK) pathway. Furthermore, the sensitivity to HT was remarkably enhanced in BAG3-downregulated HSC-3 cells. Interestingly, the effects of this combination treatment were significantly enhanced in the cells pretreated with a JNK inhibitor, SP600125. These findings indicated that the disruption of functions of both BAG3 and the JNK pathway may become an option in HT therapy in OSCC cells.

Original languageEnglish
Pages (from-to)52-57
Number of pages6
JournalCancer Letters
Volume335
Issue number1
DOIs
StatePublished - 2013/07/10

Keywords

  • Apoptosis
  • BAG3
  • Hyperthermia
  • JNK pathway

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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