Tumor Necrosis Factor and Cytotoxic Agents: Effect on Squamous Carcinoma Lines

Abstract

The cytotoxicity of dactinomycin (actinomycin D), doxorubicin hydrochloride (Adriamycin), cisplatin, fluorouracil, and methotrexate alone and in combination with recombinant human tumor necrosis factor (rHuTNF) on human squamous cell carcinoma lines was studied by an MTT proliferation assay. The rHuTNF alone caused no inhibition after 24 to 72 hours. All lines investigated showed a dose-dependent response to dactinomycin and doxorubicin. Potentiation of dactinomycin and doxorubicin cytotoxicity occurred with four of six cell lines following incubation of rHuTNF and the drug. No synergistic effect on cytotoxicity was seen with rHuTNF and any chemotherapeutic agent on two cell lines. The addition of rHuTNF did not augment the cytotoxic effect seen with cisplatin, methotrexate, or fluorouracil on any cell line. These results show that rHuTNF can enhance the cytotoxic effect of certain chemotherapeutic agents on squamous cell lines in vitro.

Inhibition of transcription factor nuclear factor-κB by a mutant inhibitor-κBα attenuates resistance of human head and neck squamous cell carcinoma to TNF-α caspase-mediated cell death

“…In the present study, we confirmed that the 3 human UM-SCC cell lines previously shown to exhibit constitutive activation of NF-κB are highly resistant to TNF-α induced cell death. Our results which demonstrate a relatively high resistance of these 3 UM-SCC cell lines to TNF-α cytotoxicity are consistent with several studies with different panels of cell lines, which showed that resistance of HNSCC to TNF-α is common (Gapany et al, 1990, Schuger et al, 1990, Sacchi et al, 1991, Monchimatsu et al, 1993, Briskin et al, 1996. The UM-SCC cell lines in the present study exhibited limited sensitivity at 10 4 U/ml TNF-α, consistent with results obtained in another laboratory with a different panel of HNSCC cell lines (Briskin et al, 1996).…”

“…TNF-α has been shown to induce cell death of tumours via apoptosis or necrosis (Schmid et al, 1986;Dealtry et al, 1987;Larrick and Wright, 1990;Laster et al, 1998). TNF-α can induce apoptosis of some HNSCC cell lines at concentrations at or above 10 4 U/ml (Briskin et al, 1996), but most human HNSCC have been reported to be relatively resistant to TNF-α (Gapany et al, 1990, Schuger et al, 1990Sacchi et al, 1991, Monchimatsu et al, 1993, Briskin et al, 1996. Development of resistance to TNF-α has been shown to occur with tumour progression in murine fibrosarcomas through exposure of tumour cells to TNF-α produced by host responses, and selection of TNF-α resistant tumour cells (Urban et al, 1983(Urban et al, , 1986).…”

The sensitivity of head and neck squamous cell carcinomas to tumor necrosis factor-α

“…Alexander et al [17] explain the synergistic effect of TNF-a and chemotherapeutic drugs by damaging DNA topoisomerase of tumor cells. Gapany et al [18] have also exhibited the synergistic effects of TNF-a with actinomycin-D or adriamycin, whereas there is no synergistic effect of TNF-a with CDDP, 5-fluorouracil (5-Fu) nor MTX. Furthermore, Douglas et al [19] have reported that interferon-T significantly enhances the cytolytic activity of TNF-a in the presence of actinomycin-D or adriamycin.…”