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

Tumour Biol. 2005 Jul-Aug;26(4):165-72. doi: 10.1159/000086949. Epub 2005 Jul 6.

Abstract

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, Neoplasm / genetics
  • Antigens, Neoplasm / metabolism*
  • Apoptosis / drug effects
  • Apoptosis / physiology*
  • Carcinoma, Squamous Cell / metabolism*
  • Caspase 9
  • Caspases / metabolism
  • Cell Line, Tumor
  • Cytochromes c / metabolism*
  • Dose-Response Relationship, Drug
  • Humans
  • Immunoblotting
  • Immunohistochemistry
  • Mitochondria / metabolism
  • Mouth Neoplasms / metabolism*
  • RNA, Messenger / analysis
  • Reverse Transcriptase Polymerase Chain Reaction
  • Serpins / genetics
  • Serpins / metabolism*
  • Transfection
  • Tumor Necrosis Factor-alpha / metabolism
  • Tumor Necrosis Factor-alpha / pharmacology

Substances

  • Antigens, Neoplasm
  • RNA, Messenger
  • Serpins
  • Tumor Necrosis Factor-alpha
  • squamous cell carcinoma-related antigen
  • Cytochromes c
  • CASP9 protein, human
  • Caspase 9
  • Caspases