The
Fas receptor is a potentially valuable therapeutic target in
cancer treatment. However, the clinical application of
antibodies directed to this target is hindered by their serious side effects in vivo, including liver toxicity. One murine
monoclonal antibody, mHFE7A, binds both to human Fas and murine Fas, without inducing any obvious side effects. However, the potential
therapeutic effects of mHFE7A are unclear in human
cancer cells or
tumors. Here, we determined whether mHFE7A could induce apoptosis in vitro, and assessed its effects on major apoptotic pathways in a human
melanoma cell line, MMN9. We also investigated its anti-
cancer effects on transplanted
melanoma MMN9
tumors in BALB/c nude mice. Treatment of mHFE7A cross-linking with Ig induced cell death similar to CH-11 treatment. Apoptosis induced by mHFE7A was defined by
Hoechst 33342 DNA staining and DNA fragmentation assay. Furthermore, mHFE7A-mediated apoptosis was dependent on activation of a
caspase signaling cascade involving caspases-8 and -3. Administration of mHFE7A also delayed the growth of
melanoma xenografts. Thus, we provide the first evidence that the murine
anti-Fas monoclonal antibody, mHFE7A, induces apoptosis of human
malignant melanoma cells in vitro and is anti-tumorigenic in vivo.