Enhanced Susceptibility to Fas-mediated Apoptosis by Interferon-γ in an Oral Squamous Cell Carcinoma Cell Line

Abstract

Fas is widely expressed on the cell surface of many normal and neoplastic cells and induces apoptotic cell death in the presence of Fas ligand (FasL) or Fas-agonistic antibody CH11 (Fas-mediated apoptosis) Cancer cells constitutively expressing Fas are generally resistant to Fas-mediatedapoptosis. Recently, it has been reported that interferon-ƒÁ (IFN-ƒÁ) enhances Fas-mediated apoptosis. An oral squamous cell carcinoma cell line, NA, also constitutively expresses Fas on the plasma membrane and shows low susceptibility to Fas-agonistic antibody-induced apoptosis. This study was conducted to examine the effects of IFN-ƒÁy on Fas-mediated apoptosis, the expression of Fas and FasL, and the production of soluble Fas (sFas) in NA cells. The results revealed that a Fas-agonistic antibody, CH11, induced apoptosis of NA cells and IFN-ƒÁ enhanced susceptibility of NA cells to CH11-induced apoptosis. Further more, IFN-ƒÁ up-regulated Fas expression on NA cells without affecting the expression of FasL. A slight decrease in sFas expression was induced by treatment with IFN-ƒÁ. These results suggest that IFN-ƒÁ may enhance the susceptibility of NA cells to Fas-mediated apoptosis through the up-regulation of Fas.