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.
Hashimoto
Ken-ichiro
K
Section of Oral Oncology, Department of Oral and Maxillofacial Surgery, Fukuoka Dental College, Fukuoka, Japan.
Kiyoshima
Tamotsu
T
Matsuo
Kou
K
Ozeki
Satoru
S
Sakai
Hidetaka
H
D000951:Antigens, Neoplasm / Q000235:genetics / Q000378:metabolism*; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D002294:Carcinoma, Squamous Cell / Q000378:metabolism*; D053453:Caspase 9; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D045304:Cytochromes c / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D008928:Mitochondria / Q000378:metabolism; D009062:Mouth Neoplasms / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015843:Serpins / Q000235:genetics / Q000378:metabolism*; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism / Q000494:pharmacology
D000951:Antigens, Neoplasm; D012333:RNA, Messenger; D015843:Serpins; D014409:Tumor Necrosis Factor-alpha; C051072:squamous cell carcinoma-related antigen; D045304:Cytochromes c; C506433:CASP9 protein, human; D053453:Caspase 9; D020169:Caspases