The effect of cyclophosphamide on Fas-mediated apoptosis.

Fas is a cell surface protein that can mediate apoptosis and belongs to the tumor necrosis factor (TNF) receptor family. Anti-Fas antibody induces apoptotic cell death in sensitive cells. Because many chemotherapeutic drugs are capable of initiating pathways leading to apoptosis, we determined the effect of cyclophosphamide, one of the most widely used anticancer drugs, on Fas mediated apoptosis in human lymphoma cell lines; SKW6.4 and Jurkat. Cell lines were cultured for 3 days alone in a medium or with cyclophosphamide (2 micrograms/ml). Anti-Fas IgM of various concentrations was added after treatment. Apoptosis was measured by electrophoresis of DNA fragmentation and surface expression of Fas was measured by flow cytometry. These cell lines were found to express Fas and were very sensitive to anti-Fas induced by cyclophosphamide in Jurkat except SKW6.4. Cyclophosphamide augumented apoptosis mediated by anti-Fas, synergistically. These results suggested that the anti-cancer drug might be mediated via the pathway of Fas mediated apoptosis in the lymphoma cell lines.