Abstract

The analysis of the lytic mechanism initiated by TNFα 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 TNFα in L929 cells. In addition to being independent of protein synthesis, the lytic mechanism initiated by TNFα 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 TNFα 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 TNFα-mediated lysis. Using DNA-specific staining (DAPI and Apoptag) it was shown that when the human ovarian and cervical carcinoma cells are lysed by TNFα, death occurs via apoptosis.

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