Characterization of the protein synthesis independent TNFalpha lytic mechanism in human ovarian and cervical carcinoma cell lines.

The analysis of the lytic mechanism initiated by TNFalpha in three human ovarian cell lines (CAOV-3, SK-OV-3, and OVCAR-3) and in three human cervical cell lines (SIHa, HT-3, and ME-180) in the presence of inhibitors of protein synthesis indicates that this lytic mechanism is similar to the protein synthesis-independent lytic mechanism initiated by TNFalpha in L929 cells. In addition to being independent of protein synthesis, the lytic mechanism initiated by TNFalpha in human ovarian and cervical carcinoma cells is also not dependent on the formation of oxygen radicals, as shown by the inability of the oxygen radical scavengers DMSO or glutathione to inhibit lysis. In spite of the fact that oxygen radicals are not involved in lysis, the TNFalpha lytic mechanism initiated in the human ovarian and cervical carcinoma cells is dependent on the activity of lipoxygenase enzymes. This was shown by the ability of the lipoxygenase enzyme inhibitor, NDGA, to block TNFalpha-mediated lysis. Using DNA-specific staining (DAPI and Apoptag) it was shown that when the human ovarian and cervical carcinoma cells are lysed by TNFalpha, death occurs via apoptosis.