Effect of SCCA1 and SCCA2 on the suppression of TNF-α-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-α-induced cell death in human oral squamous cell carcinoma cell lines. The viability of MISK81-5 and sMISK cells treated with TNF-α dose-dependently decreased. The sMISK cells which stably overexpressed SCCA1 and SCCA2 cDNA showed a greater resistance against the cell death induced by TNF-α than the controls. Immunocytochemical staining for cytochrome c showed a punctate pattern in the cytoplasm of the TNF-α-untreated cells. After treatment with TNF-α, 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-α 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-α-induced cell death in vitro, by inhibiting the release of mitochondrial cytochrome c to some degree.