Effect of naturally occurring organosulfur compounds on nitric oxide production in lipopolysaccharide-activated macrophages.
Excessive nitric oxide (NO) production is involved in cellular injury and possibly in the multistage process of carcinogenesis. In this study, we investigated the effect of organosulfur compounds (S-allyl cysteine, allyl sulfide, diallyl disulfide, allyl isothiocyanate, phenyl isothiocyanate, and benzyl isothiocyanate) that are found in allium or cruciferous vegetables on NO production in J774.1 macrophages activated with lipopolysaccharide (LPS). Diallyl disulfide, allyl, phenyl, and benzyl isothiocyanates inhibited NO production, as evaluated by nitrite formation at 25 microM. Allyl and benzyl isothiocyanates, the most active of the six organosulfur compounds, exhibited dose-dependent inhibition and had IC(50) values of 1.6 and 2.7 microM, respectively. Western blot analysis suggested that suppression of the induction of inducible NO synthase (iNOS) expression is responsible for the inhibition of NO production by allyl and benzyl isothiocyanates. In contrast, these isothiocyanates increased LPS-stimulated tumor necrosis factor alpha (TNF-alpha) release, suggesting their selective action on genes activated by LPS. Our results demonstrate that certain organosulfur compounds inhibit NO synthesis in LPS-activated macrophages, and the inhibitory effect may be a significant component of their anticarcinogenic activity.
Ippoushi
Katsunari
K
National Institute of Vegetable and Tea Science, National Agricultural Research Organization, 514-2392 Ano, Mie, Japan. ippoushi@affrc.go.jp
Itou
Hidekazu
H
Azuma
Keiko
K
Higashio
Hisao
H
D000498:Allyl Compounds / Q000494:pharmacology; D000818:Animals; D002478:Cells, Cultured; D003545:Cysteine / Q000031:analogs & derivatives* / Q000494:pharmacology; D004347:Drug Interactions; D015870:Gene Expression / Q000187:drug effects; D017879:Isothiocyanates / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D051379:Mice; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000096:biosynthesis; D052247:Nitric Oxide Synthase Type II; D013440:Sulfides / Q000494:pharmacology; D013457:Sulfur Compounds / Q000737:chemistry / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000498:Allyl Compounds; D017879:Isothiocyanates; D008070:Lipopolysaccharides; D013440:Sulfides; D013457:Sulfur Compounds; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; C038491:allyl sulfide; C065299:S-allylcysteine; C031403:benzyl isothiocyanate; C004471:allyl isothiocyanate; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D003545:Cysteine