Comparison of TNFα and TNFβ Cytolytic Mechanisms in Human Ovarian and Cervical Carcinoma Cell Lines

Abstract

Objectives.The aim of this study was to determine the potential and mechanism of tumor necrosis factor β (TNFβ) mediated cytolysis in human ovarian and cervical carcinoma cells.Methods.The cytolytic potential of tumor necrosis factor α (TNFα) and TNFβ 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 TNFα-mediated cytolysis in these cells. The effects of these agents on TNFβ-mediated cytolysis were determined.Results.All of the cell lines express a protein-synthesis-dependent TNFα and TNFβ resistance mechanisms. When protein synthesis is inhibited the cytolytic activity of TNFβ was fivefold greater than that of TNFα in L929 cells. In contrast, the cytolytic activity of TNFα was fivefold greater than that of TNFβ in the human cells. Like the TNFα cytolytic mechanism, the TNFβ 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 TNFβ in human cells. The fact that the cytolytic mechanism of TNFβ appears very similar to that of TNFα could be important to our understanding of the potential of these closely related cytokines in anticancer therapies. Although the cytolytic potential of TNFβ is greater than that of TNFα in mouse cells, this is not true in human cells and could limit the efficacy of TNFβ in anticancer therapies.