Synergistic effect of human immune interferon and double-stranded RNA against human colon carcinoma cells in vitro.
The cytocidal activity of human immune interferon (IFN-gamma) in combination with the synthetic double-stranded RNA, poly(I).poly(C), was investigated in human colon carcinoma cell line HT-29. Three days of treatment with IFN-gamma (10 to 25 units/ml) resulted in 30 to 40% reduction in colony formation, whereas poly(I).poly(C) (25 to 100 micrograms/ml) reduced cell viability by 10 to 20% of control. The lethal effect of the combination of IFN-gamma and poly(I).poly(C) was synergistic wherein 70 to 90% reduction in colony formation was observed. Measurements of DNA, RNA, and protein synthesis after IFN-gamma and poly(I).poly(C) treatment showed a dose-dependent reduction in all three parameters. Recombinant IFN-gamma in combination with poly(I).poly(C) exhibited a similar effect. Studies evaluating the molecular mechanism of IFN-gamma and poly(I).poly(C) toxicity indicate a lack of involvement of the double-stranded RNA-dependent (2',5')oligoadenylate-RNase L and protein kinase pathways; however, the effect appears to be related to the inhibition of ribosomal RNA transcription in this cell line.
D015088:2',5'-Oligoadenylate Synthetase / Q000032:analysis; D000227:Adenine Nucleotides / Q000032:analysis; D000906:Antibodies / Q000276:immunology; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003110:Colonic Neoplasms / Q000378:metabolism / Q000628:therapy*; D004357:Drug Synergism; D006801:Humans; D007371:Interferon-gamma / Q000008:administration & dosage*; D009696:Nucleic Acids / Q000096:biosynthesis; D009843:Oligoribonucleotides / Q000032:analysis; D011070:Poly I-C / Q000494:pharmacology; D014176:Protein Biosynthesis; D012330:RNA, Double-Stranded / Q000008:administration & dosage*; D012335:RNA, Ribosomal / Q000096:biosynthesis
D000227:Adenine Nucleotides; D000906:Antibodies; D009696:Nucleic Acids; D009843:Oligoribonucleotides; D012330:RNA, Double-Stranded; D012335:RNA, Ribosomal; C023505:2',5'-oligoadenylate; D007371:Interferon-gamma; D015088:2',5'-Oligoadenylate Synthetase; D011070:Poly I-C