title: The combination of silencing BAG3 and inhibition of the JNK pathway enhances hyperthermia sensitivity in human oral squamous cell carcinoma cells.
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.
authors: Department of Radiological Sciences, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan. yunokiki@med.u-toyama.ac.jp
authors: Tatsuya
authors: T
authors: Yunoki
authors: Ayako
authors: A
authors: Kariya
authors: Takashi
authors: T
authors: Kondo
authors: Atsushi
authors: A
authors: Hayashi
authors: Yoshiaki
authors: Y
authors: Tabuchi
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics* / Q000378:metabolism; D000873:Anthracenes / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins; D002294:Carcinoma, Squamous Cell / Q000378:metabolism*; D045744:Cell Line, Tumor; D055785:Gene Knockdown Techniques; D018869:Heat-Shock Response; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D009062:Mouth Neoplasms / Q000378:metabolism*; D034622:RNA Interference; D015533:Transcriptional Activation
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000873:Anthracenes; D000970:Antineoplastic Agents; D051017:Apoptosis Regulatory Proteins; C414431:BAG3 protein, human; C432165:pyrazolanthrone; D048031:JNK Mitogen-Activated Protein Kinases