Actinomycin D Induces Hepatocyte Cell Death and Upregulation of FADD/MORT1

. We have studied ligand-dependent apoptosis via the tumor necrosis factor (TNF) receptor in hepatocytes. (1) These experiments require the addition of actinomycin D (ActD) to kill cells because TNF alone does not kill rat hepatocytes in culture. FADD/MORT1 (fas-associated death domain protein) is an intracellular protein that mediates activation of proteases called caspases which are critical to the propagation of the apoptotic signaling cascade. (2) Because of its pivotal role in the cell death pathway of multiple receptors (3), we believe that the regulation of FADD may have profound effects on the modulation of cell death. We have studied the effects of actinomycin D on FADD in primary rat hepatocyte cultures in order to elucidate the molecular pathways of cell death that may be altered or manipulated in cancer.