[Inhibitory effects of interferon and inhibitors of polyamine biosynthesis on clonal growth of Raji cells derived from Burkitt's lymphoma].
Interferon (IFN)-alpha, -gamma, and two inhibitors of polyamine biosynthesis (alpha-difluoromethyl ornithine; DFMO and methyl glyoxal bis-guanyl hydrazone; MGBG) inhibited the clonal growth of Raji cells. The combination-treatment using two agents, particularly IFN-alpha and DFMO represented synergistic effects. In order to investigate the mechanism of the synergism between IFNs and inhibitors of polyamine biosynthesis, the concentrations of polyamines and the levels of 2'-5' oligo-adenylate synthetase (2-5 AS) activity in the treated Raji cells were determined. Not only the inhibitors of polyamine biosynthesis, but also IFNs decreased the content of spermidine in the cells. Furthermore, the clonogenic growth-inhibition by IFN-alpha was recovered partially by exogenous spermidine. On the other hand, 2-5AS activity in the cells was elevated to 57 times by the treatment with interferon-alpha and further more, the combinations of IFN and the inhibitors of polyamine biosynthesis induced higher activities of 2-5AS as compared with those by each agent. From these results, it was suggested that the synergistic effects of IFNs in combinations with inhibitors of polyamine biosynthesis on the inhibition of clonal growth of Raji cells were closely associated with the decrease of intracellular polyamine level and the increase of 2-5AS activity in the treated cells.
Kamada
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Third Department of Internal Medicine, Hokkaido University School of Medicine, Sapporo, Japan.
D015088:2',5'-Oligoadenylate Synthetase / Q000378:metabolism; D015317:Biogenic Polyamines / Q000096:biosynthesis*; D002051:Burkitt Lymphoma / Q000473:pathology*; D003114:Colony-Forming Units Assay; D003864:Depression, Chemical; D004357:Drug Synergism; D000518:Eflornithine / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D007370:Interferon Type I / Q000008:administration & dosage / Q000494:pharmacology*; D007371:Interferon-gamma / Q000008:administration & dosage / Q000494:pharmacology*; D008935:Mitoguazone / Q000008:administration & dosage / Q000494:pharmacology*; D011994:Recombinant Proteins; D014407:Tumor Cells, Cultured
D015317:Biogenic Polyamines; D007370:Interferon Type I; D011994:Recombinant Proteins; D007371:Interferon-gamma; D015088:2',5'-Oligoadenylate Synthetase; D008935:Mitoguazone; D000518:Eflornithine