Comparison of TNFalpha and TNFbeta cytolytic mechanisms in human ovarian and cervical carcinoma cell lines.

OBJECTIVES

The aim of this study was to determine the potential and mechanism of tumor necrosis factor beta (TNFbeta) mediated cytolysis in human ovarian and cervical carcinoma cells.

METHODS

The cytolytic potential of tumor necrosis factor alpha (TNFalpha) and TNFbeta was determined using the TNF reference cell line L929 and human ovarian (SK-OV-3, CaOV-3) and cervical (SiHa, HT-3) carcinoma cell lines. We have previously reported the effects of the lipoxygenase enzyme inhibitor, nordihydroguaiaretic acid, the oxygen radical scavenger glutathione, and fragmented DNA-specific staining with diamidino-2-phenylindole and ApopTag on TNFalpha-mediated cytolysis in these cells. The effects of these agents on TNFbeta-mediated cytolysis were determined.

RESULTS

All of the cell lines express a protein-synthesis-dependent TNFalpha and TNFbeta resistance mechanisms. When protein synthesis is inhibited the cytolytic activity of TNFbeta was fivefold greater than that of TNFalpha in L929 cells. In contrast, the cytolytic activity of TNFalpha was fivefold greater than that of TNFbeta in the human cells. Like the TNFalpha cytolytic mechanism, the TNFbeta cytolytic mechanism is dependent on lipoxygenase enzymes, but not oxygen radicals, and results in apoptosis.

CONCLUSIONS

To date there is little information about the cytolytic potential of TNFbeta in human cells. The fact that the cytolytic mechanism of TNFbeta appears very similar to that of TNFalpha could be important to our understanding of the potential of these closely related cytokines in anticancer therapies. Although the cytolytic potential of TNFbeta is greater than that of TNFalpha in mouse cells, this is not true in human cells and could limit the efficacy of TNFbeta in anticancer therapies.