Potentiation of the cytocidal effect of human immune interferon by different synthetic double-stranded RNAs in the refractory human colon carcinoma cell line BE.
A human cell line BE, derived from an undifferentiated carcinoma of the colon, was studied for its response to the cytocidal effects of human immune interferon (IFN-gamma) alone and in combination with various double-standard RNAs (dsRNAs). BE cells were moderately refractory to 3-day treatment with IFN-gamma (10 to 300 units/ml) where only 5 to 30% reduction in colony formation occurred. A similar exposure interval to polyriboinosinic.polyribocytidylic acid [poly(I).poly(C)] (100 micrograms/ml) had no detectable effect on colony formation. In contrast, the lethal effect of the combination of IFN-gamma and poly(I).poly(C) was synergistic and this regimen produced a 40 to 80% reduction in colony formation. The cytocidal effects of the combination of IFN-gamma with varying concentrations of the dsRNAs poly(I).poly(C), polyriboadenylic.polyribouridylic acid [poly(A).poly(U)], polyriboinosinic.polyribocytidylic acid stabilized with poly-L-lysine in carboxymethylcellulose [poly(ICLC)], and mismatched dsRNA [rIn.r(C13,U)n] were also examined. The concentration of the dsRNAs producing a 50% decrease in cell viability in combination with IFN-gamma (100 units/ml) was 6 micrograms/ml for poly(I).poly(C), 1 microgram/ml for poly(A).poly(U), 3 ng/ml for poly(ICLC), and 16 micrograms/ml for rIn.r(C13,U)n. DNA, RNA, and protein synthesis in IFN-gamma and poly(I).poly(C)-treated cells were reduced in a dose-dependent manner. However, there were no changes in either (2',5')oligoadenylate concentrations or in ribosomal RNA transcription following treatment with IFN-gamma and poly(I).poly(C). Thus, the synergism resulting from the combination of IFN-gamma and dsRNA appears to be mediated via another, as yet unknown, mechanism.
Chapekar
M S
MS
Glazer
R I
RI
D015088:2',5'-Oligoadenylate Synthetase / Q000032:analysis; D000227:Adenine Nucleotides / Q000032:analysis; D002266:Carboxymethylcellulose Sodium / Q000494:pharmacology / Q000031:analogs & derivatives; D002277:Carcinoma / Q000473:pathology*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D003110:Colonic Neoplasms / Q000473:pathology*; D004273:DNA, Neoplasm / Q000096:biosynthesis; D004357:Drug Synergism; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology*; D009363:Neoplasm Proteins / Q000096:biosynthesis; D009843:Oligoribonucleotides / Q000032:analysis; D011063:Poly A-U / Q000494:pharmacology; D011070:Poly I-C / Q000494:pharmacology; D011107:Polylysine / Q000494:pharmacology / Q000031:analogs & derivatives; D012330:RNA, Double-Stranded / Q000494:pharmacology*; D012334:RNA, Neoplasm / Q000096:biosynthesis; D012335:RNA, Ribosomal / Q000096:biosynthesis
D000227:Adenine Nucleotides; D004273:DNA, Neoplasm; D009363:Neoplasm Proteins; D009843:Oligoribonucleotides; D012330:RNA, Double-Stranded; D012334:RNA, Neoplasm; D012335:RNA, Ribosomal; D011063:Poly A-U; D011107:Polylysine; C023505:2',5'-oligoadenylate; C019531:poly ICLC; D007371:Interferon-gamma; D015088:2',5'-Oligoadenylate Synthetase; D002266:Carboxymethylcellulose Sodium; D011070:Poly I-C