Synergistic cytotoxic effects of recombinant human tumor necrosis factor, interferons, and heat-stress.
A synergistic increase in the cytotoxic effects of recombinant human tumor necrosis factor (TNF-alpha), interferons (IFN-alpha, IFN-beta, and IFN-gamma) and heat-stress was demonstrated in vitro. The toxicity of these agents was assessed in the human cervical carcinoma HeLa cell line: the toxic effect was greatly increased when cells pretreated with IFNs or TNF were submitted to a 1-h heat-shock at 45 degrees C. Moreover if the heat-stress followed simultaneous treatment with both cytokines, a synergistic effect between these treatments could be observed. The same observations were made for two other transformed cell lines: the oral epidermoid carcinoma KB cells and the hepatocarcinoma PLC/PRF/5 cells. In contrast, the survival of normal cells (normal foetal lung MRC5 cells and foreskin F 7000 fibroblasts) was only slightly decreased by such treatments. These results suggest that combining a heat-stress with cytokines treatment might be one way of enhancing the sensitivity of cancer cells to the growth inhibitory effects of the individual cytokines.
Dubois
M F
MF
INSERM U 43, Hôpital Saint-Vincent de Paul, Paris, France.
Ferrieux
C
C
Lebon
P
P
D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004357:Drug Synergism; D006367:HeLa Cells; D006358:Hot Temperature; D006801:Humans; D066298:In Vitro Techniques; D007372:Interferons / Q000633:toxicity*; D014409:Tumor Necrosis Factor-alpha / Q000633:toxicity*
D014409:Tumor Necrosis Factor-alpha; D007372:Interferons