کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
5512887 1540626 2017 9 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Nobiletin and its colonic metabolites suppress colitis-associated colon carcinogenesis by down-regulating iNOS, inducing antioxidative enzymes and arresting cell cycle progression
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شیمی
پیش نمایش صفحه اول مقاله
Nobiletin and its colonic metabolites suppress colitis-associated colon carcinogenesis by down-regulating iNOS, inducing antioxidative enzymes and arresting cell cycle progression
چکیده انگلیسی
Nobiletin (NOB) is a major citrus polymethoxyflavone (PMF) with various beneficial biological activities. We reported previously that dietary NOB significantly inhibited colitis-associated colon carcinogenesis in azoxymethane (AOM)/dextran sulfate sodium (DSS)-treated mice, and the chemopreventive effects were associated with NOB metabolites found in the mouse colonic tissues. In this study, to better understand the role of colonic metabolites of NOB, we determined the anti-inflammation and anticancer effects of a mixture of NOB and its major metabolites (NOB-Met) at the concentrations equivalent to those found in colonic tissues of NOB-fed mice. The results demonstrated that NOB-Met effectively decreased the expression level of inducible nitric oxide synthase (iNOS), increased the level of heme oxygenase-1 (HO-1) and NADH quinone oxidoreductase 1 (NQO1) and up-regulated nuclear factor erythroid 2-related factor (Nrf2) signaling pathway in lipopolysaccharide (LPS)-stimulated macrophages. NOB-Met also caused a significant cell cycle arrest in human colon cancer cells. Validation study confirmed that dietary NOB led to the effects similar to those described above in the colon of AOM/DSS-treated mice. Specifically, dietary NOB significantly reduced the level of iNOS, up-regulated Nrf2-dependent enzymes and profoundly modulated key signaling proteins resulting in decreased cell cycle progression in the colonic tissue of AOM/DSS-treated mice. Overall, our findings demonstrated that dietary NOB led to the presence of NOB and its metabolites in the colonic tissue, which suppressed colitis-associated colon carcinogenesis via down-regulating iNOS, inducing antioxidative enzymes and arresting cell cycle progression.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: The Journal of Nutritional Biochemistry - Volume 42, April 2017, Pages 17-25
نویسندگان
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