CHARACTERIZATION OF THE PROTEIN-SYNTHESIS INDEPENDENT TNF-ALPHA LYTICMECHANISM IN HUMAN OVARIAN AND CERVICAL-CARCINOMA CELL-LINES

The analysis of the lytic mechanism initiated by TNF alpha in three hu man ovarian cell lines (CAOV-3, SK-OV-3, and OVCAR-3) and in three hum an cervical cell lines (SIHa, HT-3, and ME-180) in the presence of inh ibitors of protein synthesis indicates that this lytic mechanism is si milar to the protein synthesis-independent lytic mechanism initiated b y TNF alpha in L929 cells. In addition to being independent of protein synthesis, the lytic mechanism initiated by TNF alpha in human ovaria n and cervical carcinoma cells is also not dependent on, the formation of oxygen radicals, as shown by the inability of the oxygen radical s cavengers DMSO or glutathione to inhibit lysis. In spite of the fact t hat oxygen radicals are not involved in lysis, the TNF alpha lytic mec hanism initiated in the human ovarian and cervical carcinoma cells is dependent on the activity of Lipoxygenase enzymes. This was shown by t he ability of the lipoxygenase enzyme inhibitor, NDGA, to block TNF al pha-mediated lysis, Using DNA-specific staining (DAPI and Apoptag) it mas shown that when the human ovarian and cervical carcinoma cells are lysed by TNF alpha, death occurs Pia apoptosis. (C) 1996 Academic Pre ss, Inc.