C B Powell1, J H Scott, J L Collins. 1. Division of Gynecologic Oncology, University of California/Mount Zion Medical Center, San Francisco, California, 94120, USA.
Abstract
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. Copyright 1998 Academic Press.
OBJECTIVES: The aim of this study was to determine the potential and mechanism of tumor necrosis factor beta (TNFbeta) mediated cytolysis in humanovarian 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. Copyright 1998 Academic Press.
Authors: Nicolae-Costin Diaconu; Jaana Rummukainen; Mikko Mättö; Anita Naukkarinen; Rauno J Harvima; Jukka Pelkonen; Ilkka T Harvima Journal: BMC Cancer Date: 2008-02-07 Impact factor: 4.430