Synergistic effect of human immune interferon and double-stranded RNA against human colon carcinoma cells in vitro.

Abstract

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.

• Authors: M S Chapekar, R I Glazer
• Journal: Cancer research (Cancer Res) Vol. 45 Issue 6 Pg. 2539-44 (Jun 1985) ISSN: 0008-5472 [Print] United States
• PMID: 3921246 (Publication Type: Journal Article)

Chemical References

• Adenine Nucleotides
• Antibodies
• Nucleic Acids
• Oligoribonucleotides
• RNA, Double-Stranded
• RNA, Ribosomal
• 2',5'-oligoadenylate
• Interferon-gamma
• 2',5'-Oligoadenylate Synthetase
• Poly I-C

Topics

• 2',5'-Oligoadenylate Synthetase (analysis)
• Adenine Nucleotides (analysis)
• Antibodies (immunology)
• Cell Survival (drug effects)
• Cells, Cultured
• Colonic Neoplasms (metabolism, therapy)
• Drug Synergism
• Humans
• Interferon-gamma (administration & dosage)
• Nucleic Acids (biosynthesis)
• Oligoribonucleotides (analysis)
• Poly I-C (pharmacology)
• Protein Biosynthesis
• RNA, Double-Stranded (administration & dosage)
• RNA, Ribosomal (biosynthesis)