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  • Title: Inhibition of LPS-stimulated NO production in mouse macrophage-like cells by tropolones.
    Author: Yokoyama K, Hashiba K, Wakabayashi H, Hashimoto K, Satoh K, Kurihara T, Motohashi N, Sakagami H.
    Journal: Anticancer Res; 2004; 24(6):3917-22. PubMed ID: 15736432.
    Abstract:
    We investigated the effect of 27 tropolones on nitric oxide (NO) production by mouse macrophage-like Raw 264.7 cells. All of these compounds failed to stimulate the Raw 264. 7 cells to produce detectable amounts of NO, but inhibited NO production by lipopolysaccharide (LPS)-activated Raw 264.7 cells to various extents. Generally, the ability of tropolones to inhibit LPS-stimulated NO production was inversely related to their cytotoxic activity. Western blot and RT-PCR analyses demonstrated that the most active compound, 2,4-dibromo-7-methoxytropone [21], significantly reduced both the intracellular concentration of iNOS protein and the expression of iNOS mRNA. ESR spectroscopy showed that [21] did not produce radicals under alkaline condition, nor scavenged NO, produced by NOC-7. These data suggested that the inhibitory effect of [21] on NO production might be generated via the inhibition of iNOS expression, rather than a radical-mediated mechanism.
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