Comparison of TNF alpha and TNF beta cytolytic mechanisms in human ovarianand cervical carcinoma cell lines

Objectives. The aim of this study was to determine the potential and mechan ism of tumor necrosis factor beta (TNF beta) mediated cytolysis in human ov arian and cervical carcinoma cells. Methods. The cytolytic potential of tumor necrosis factor alpha (TNF alpha) and TNF beta was determined using the TNF reference cell line L929 and hum an ovarian (SK-OV-3, CaOV-3) and cervical (SiHa, HT-3) carcinoma cell lines . We have previously reported the effects of the lipoxygenase enzyme inhibi tor, nordihydroguaiaretic acid, the oxygen radical scavenger glutathione, a nd fragmented DNA-specific staining with diamidino-2-phenylindole and ApopT ag on TNF alpha-mediated cytolysis in these cells. The effects of these age nts on TNF beta-mediated cytolysis were determined. Results. All of the cell lines express a protein-synthesis-dependent TNF al pha and TNF beta resistance mechanisms. When protein synthesis is inhibited the cytolytic activity of TNF beta was fivefold greater than that of TNF a lpha in L929 cells, In contrast, the cytolytic activity of TNF alpha was fi vefold greater than that of TNF beta in the human cells. Like the TNF alpha cytolytic mechanism, the TNF beta cytolytic mechanism is dependent on lipo xygenase enzymes, but not oxygen radicals, and results in apoptosis. Conclusions. To date there is little information about the cytolytic potent ial of TNF beta in human cells, The fact that the cytolytic mechanism of TN F beta appears very similar to that of TNF alpha could be important to our understanding of the potential of these closely related cytokines in antica ncer therapies. Although the cytolytic potential of TNF beta is greater tha n that of TNF alpha in mouse cells, this is not true in human cells and cou ld limit the efficacy of TNF beta in anticancer therapies. (C) 1998 Academi c Press.