Modulation of topoisomerase activities by tumor necrosis factor

Tumor necrosis factor alpha induces senescence and chromosomal instability in human leukemic cells

“…These findings could have important implications in the context of our study. Indeed, previous studies have documented that TNFa triggers the production of radical oxygen species (ROS) from different sources, induced the formation of 8-hydroxy-2 0 -deoxyguanosine (8oxG) DNA oxidative lesions (Park et al, 1998) as well as the formation of DNA breaks (Baloch et al, 1990;Nathan et al, 2000). Therefore, it remains quite conceivable that TNFa induced senescence by disrupting telomere structure through ROS production independently of hTERT negative regulation.…”

12-O-tetradecanoylphorbol-13-acetate-induced Apoptosis Is Mediated by Tumor Necrosis Factor α in Human Monocytic U937 Cells

“…However, it has been shown that cytotoxicity of TNF␣ is mediated through mainly TNFR1, which has a 70-amino acid region in the cytoplasmic domain termed the "death domain" (30). Further studies have found that inhibition of DNA topoisomerase, production of reactive oxygen intermediates in the mitochondria, and induction of proteases appears to be involved (31)(32)(33). It has been reported that the cytotoxic effects of TNF␣ on neoplastic cells are synergistically enhanced by TPA in vitro although the molecular mechanisms underlying this synergism are not known (34).…”

Potentiation of the anti‐tumor effect of actinomycin D by tumor necrosis factor α in mice: Correlation between in vitro and in vivo results

“…In an in vifro study on the L929 fibrosarcoma cell line, Alexander et al (1987b) showed that TNF markedly enhanced the cytotoxicity of some drugs belonging to this group, such as adriamycin, amsacrine, teniposide and etoposide, as well as Act D. Using an identical model, Utsugi et al (1990) observed that such an enhancing effect resulted from the potentiation by TNF-a of topoisomerase I-and IIassociated DNA strand breaks and from an increase of the overall activity of topoisomerases by this cytokine. However, as shown by Baloch et al (1995), modulation of topoisomerase activities by TNF-a did not correlate with the ability of this cytokine to potentiate drug-induced cytotoxicity. In our in vitro studies on MmB16 melanoma and LLI2 carcinoma, we were not able to find any synergy in the cytotoxic effect between doxorubicin (a potent topoisomerase 11-targeted agent) and TNF-a (data not shown), while TNF-a/Act D combination was highly effective against both cell lines (Fig.…”