Tumor cell-specific inhibition of inducible nitric oxide synthase activation by tiazofurin.
The effects of tiazofurin (TR) on proliferation and cytokine-induced nitric oxide (NO) production in the L929 fibrosarcoma cell line and murine embryonic fibroblasts were investigated. Treatment with TR inhibited the growth of nonconfluent L929 cells in a dose-dependent manner. TR, at concentrations not affecting cell viability or proliferation, markedly decreased IFN-gamma + LPS-induced expression of inducible NO synthase (iNOS) mRNA and, subsequently, NO production in confluent L929 cultures. However, TR did not interfere with the IFN-gamma-triggered expression of mRNA for IRF-1, an important iNOS transcription factor, implying that TR interferes with some other intracellular pathway involved in iNOS induction triggered by IFN-gamma + LPS. In contrast to the results obtained in L929 cells, iNOS mRNA expression induced by IFN-gamma + LPS in murine embryonic fibroblasts was resistant to TR, indicating a tumor-selective action of this agent.
Samardzic
T
T
Institute for Biological Research Sinisa Stankovic, Belgrade, Yugoslavia.
Stosic-Grujicic
S
S
Raicevic
N
N
Trajkovic
V
V
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000235:genetics; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D050856:Interferon Regulatory Factor-1; D007371:Interferon-gamma / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D009369:Neoplasms / Q000201:enzymology*; D009569:Nitric Oxide / Q000096:biosynthesis; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D052247:Nitric Oxide Synthase Type II; D010750:Phosphoproteins / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D012254:Ribavirin / Q000031:analogs & derivatives / Q000494:pharmacology*
D000970:Antineoplastic Agents; D004268:DNA-Binding Proteins; D004791:Enzyme Inhibitors; D050856:Interferon Regulatory Factor-1; C494258:Irf1 protein, mouse; D008070:Lipopolysaccharides; D010750:Phosphoproteins; D012333:RNA, Messenger; D009569:Nitric Oxide; D012254:Ribavirin; D007371:Interferon-gamma; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; C033706:tiazofurin