Effect of SCCA1 and SCCA2 on the suppression of TNF-alpha-induced cell death by impeding the release of mitochondrial cytochrome c in an oral squamous cell carcinoma cell line.

This study examined the effect of squamous cell carcinoma antigen 1 (SCCA1) and SCCA2 on TNF-alpha-induced cell death in human oral squamous cell carcinoma cell lines. The viability of MISK81-5 and sMISK cells treated with TNF-alpha dose-dependently decreased. The sMISK cells which stably overexpressed SCCA1 and SCCA2 cDNA showed a greater resistance against the cell death induced by TNF-alpha than the controls. Immunocytochemical staining for cytochrome c showed a punctate pattern in the cytoplasm of the TNF-alpha-untreated cells. After treatment with TNF-alpha, the punctate staining pattern was preserved in the transfectants, while this pattern disappeared in the controls. In the transfectants, the release of cytochrome c from the mitochondria to cytosol after TNF-alpha treatment was lower than in the controls. A decreased level of active caspase-9 was also observed in the transfectants. These results suggest that both SCCA1 and SCCA2 play a role in the prevention of TNF-alpha-induced cell death in vitro, by inhibiting the release of mitochondrial cytochrome c to some degree. Copyright (c) 2005 S. Karger AG, Basel.