Effects of selected food factors with chemopreventive properties on combined lipopolysaccharide- and interferon-gamma-induced IkappaB degradation in RAW264.7 macrophages.
Degradation of IkappaB (IkappaB) is a key step for nuclear factor-kappaB (NF-kappaB)-induced transcription of certain proinflammatory genes, including inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2. We selected seven chemopreventive agents and examined their effects on combined lipopolysaccharide- and interferon-gamma-induced IkappaB degradation in RAW264.7 murine macrophages. IkappaB degradation was notably suppressed by 1'-acetoxychavicol acetate (ACA), zerumbone (ZER), and benzylisothiocyanate (BITC), however, not by auraptene (AUR), while the suppressive potencies of nobiletin (NOB), genistein (GEN), and resveratrol (RES) were low, but significant. These results suggest that ACA, ZER, and BITC suppress iNOS/COX-2 gene expression mainly by attenuating IkappaB degradation, while other chemopreventive agents use alternative pathway(s) to suppress the expression of proinflammatory genes.
Murakami
Akira
A
Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Kyoto 606-8502, Japan. cancer@kais.kyoto-u.ac.jp
Matsumoto
Kazuhiko
K
Koshimizu
Koichi
K
Ohigashi
Hajime
H
D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology; D001592:Benzyl Alcohols; D002460:Cell Line / Q000378:metabolism; D003374:Coumarins / Q000494:pharmacology; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004790:Enzyme Induction / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D047309:Flavones; D005419:Flavonoids / Q000494:pharmacology; D005502:Food; D005786:Gene Expression Regulation / Q000187:drug effects*; D019833:Genistein / Q000494:pharmacology; D020672:I-kappa B Proteins / Q000235:genetics / Q000378:metabolism*; D007371:Interferon-gamma / Q000494:pharmacology*; D007527:Isoenzymes / Q000096:biosynthesis* / Q000235:genetics; D017879:Isothiocyanates / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D016328:NF-kappa B / Q000096:biosynthesis / Q000235:genetics; D019001:Nitric Oxide Synthase / Q000096:biosynthesis* / Q000235:genetics; D052247:Nitric Oxide Synthase Type II; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis* / Q000235:genetics; D000077185:Resveratrol; D012717:Sesquiterpenes / Q000494:pharmacology*; D013267:Stilbenes / Q000494:pharmacology; D013729:Terpenes / Q000494:pharmacology*; D051996:Transcription Factor RelA
D016588:Anticarcinogenic Agents; D000975:Antioxidants; D001592:Benzyl Alcohols; D003374:Coumarins; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D004791:Enzyme Inhibitors; D047309:Flavones; D005419:Flavonoids; D020672:I-kappa B Proteins; D007527:Isoenzymes; D017879:Isothiocyanates; D008070:Lipopolysaccharides; D016328:NF-kappa B; D012717:Sesquiterpenes; D013267:Stilbenes; D013729:Terpenes; D051996:Transcription Factor RelA; C403304:zerumbone; D007371:Interferon-gamma; C031403:benzyl isothiocyanate; C008661:nobiletin; D019833:Genistein; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; C105832:aurapten; D000077185:Resveratrol; C047948:1'-acetoxychavicol acetate