Induction of apoptosis by abrogation of HSP70 expression in human oral cancer cells.

We have reported differential expression of 70-kDa heat shock protein (HSP70) in human oral tumorigenesis. The functional significance of elevated levels of HSP70 protein in oral squamous cell carcinomas (SCC) remains to be elucidated. The present study was designed to investigate the role of HSP70 protein in the proliferation and survival of oral tumour cells. Abrogation of HSP70 expression by antisense HSP70 oligonucleotides treatment of human oral carcinoma cells isolated from primary tumours or HSC-2 cells triggered cell death with several characteristic features, including DNA laddering, chromatin condensation and fragmentation. Flow-cytometric analysis showed a hypodiploid DNA peak of propidium iodide-stained nuclei in the antisense oligomer-treated cells. This response was accompanied by a decrease in the percentage of cells in the S phase of the cell cycle, suggesting inhibition of cell proliferation. Treatment of oral cancer cells with HSP70 antisense oligomers resulted in decreased expression of anti-apoptotic signal protein bcl-2. Our results suggest that HSP70 antisense oligomer treatment abrogates the expression of HSP70 protein that may disrupt HSP70-bcl-2 interactions, in turn inhibiting cell proliferation and inducing apoptosis. Conversely, the data suggest that HSP70 is required for proliferation and survival of oral tumour cells. Copyright 2000 Wiley-Liss, Inc.