Induction of apoptosis in HL60 leukemic cells by anticancer drugs in combination with anti-Fas monoclonal antibody.

Some anticancer drugs kill tumor cells through the mechanism of apoptosis. Fas antigen has been generally noticed as an apoptosis-signalling receptor molecule on the surface of different cells. Recently, it has become clear that some tumor cells express Fas antigen on their surface, and apoptosis is induced in those cells by IgM-anti-Fas monoclonal antibody (IgM-anti-Fas MoAb). If it is possible to induce apoptosis in tumor cells effectively by anticancer drugs in combination with IgM-anti-Fas MoAb, then we may be able to develop a new strategy for cancer chemotherapy. HL60 human leukemic cell line was incubated with anticancer drugs adriamycin (ADM) or cytosine arabinoside (Ara-C) at different doses alone and in combination with IgM-anti-Fas MoAb. We then observed the morphologic changes of tumor cells, the DNA fragmentation by agarose gel electrophoresis, and the changes in the amount of Fas antigen expression in their cell surface by using flow cytometry. In ADM- or Ara-C-treated tumor cells, apoptotic cells increased in number time- and dose-dependently. By the combination of ADM or Ara-C with IgM-anti-Fas MoAb, the induction of apoptosis in HL60 cells was enhanced significantly. The DNA electrophoresis supported those results. The amount of Fas antigen expression was slightly increased only in cells treated with a low dose of Ara-C, not in others. Our results suggest that apoptosis is a major process of leukemic cell death induced by anticancer drugs. Furthermore, it has become clear that the combination of anticancer drugs with IgM-anti-Fas MoAb enhances leukemic cell death through apoptosis in vitro, though the mechanism remains to be resolved.