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

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 degrees 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 pre-treated 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. (c) 2013 Elsevier Ireland Ltd. All rights reserved.