ArticleFood & function2020
The chemopreventive effect of 5-demethylnobiletin, a unique citrus flavonoid, on colitis-driven colorectal carcinogenesis in mice is associated with its colonic metabolites.
Article in Food & function, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 38 citations in OpenAlex.
- Nobiletin and 5‑demethylnobiletin ameliorate hypopharyngeal squamous cell carcinoma by suppressing TGF‑β‑mediated epithelial‑mesenchymal transition.Oncology letters · 2025Article
- Dietary supplementation ofAnimal nutrition (Zhongguo xu mu shou yi xue hui) · 2025Article
- The superiority of PMFs on reversing drug resistance of colon cancer and the effect on aerobic glycolysis-ROS-autophagy signaling axis.Oncology research · 2024Article
- Article
- Citrus peel polyphenols alleviate intestinal inflammation in mice with dextran sulfate sodium-induced acute colitis.Heliyon · 2023Article
- Spatial Distribution and Antioxidant Activity of Extracts from Citrus Fruits.Antioxidants (Basel, Switzerland) · 2023Article
- Soluble Epoxide Hydrolase Contributes to Cell Senescence and ER Stress in Aging Mice Colon.International journal of molecular sciences · 2023Article
- 5-Demethylnobiletin mediates cell cycle arrest and apoptosisFrontiers in oncology · 2023Article
- 5-Demethylnobiletin Inhibits Cell Proliferation, Downregulates ID1 Expression, Modulates the NF-κB/TNF-α Pathway and Exerts Antileukemic Effects in AML Cells.International journal of molecular sciences · 2022Article
- Mannose Attenuates Colitis-Associated Colorectal Tumorigenesis by Targeting Tumor-Associated Macrophages.Journal of cancer prevention · 2022Article
- Bioactive Compounds of Citrus Fruits: A Review of Composition and Health Benefits of Carotenoids, Flavonoids, Limonoids, and Terpenes.Antioxidants (Basel, Switzerland) · 2022Review
- Identification of Xanthomicrol as a Major Metabolite of 5-Demethyltangeretin in Mouse Gastrointestinal Tract and Its Inhibitory Effects on Colon Cancer Cells.Frontiers in nutrition · 2020Article
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 2 countries.
Funding
Abstract
5-Demethylnobiletin (5DN) is a unique flavonoid mainly found in citrus fruits. In this study, we determined the chemopreventive effects of 5DN and its major colonic metabolites on both a colitis-driven colon carcinogenesis mouse model and a human colon cancer cell model. In azoxymethane/dextran sulfate sodium-treated mice, dietary 5DN (0.05% w/w in the diet) significantly decreased the tumor incidence, multiplicity and burden, and showed potent anti-proliferative, proapoptotic, and anti-inflammatory activities in mouse colon tissue. Three major metabolites of 5DN, named 5,3'-didemethylnobiletin (M1), 5,4'-didemethylnobiletin (M2) and 5,3',4'-tridemethylnobiletin (M3), were found in the colonic mucosa of 5DN-treated mice, and the combined level of these metabolites in mouse colonic mucosa was 1.56-fold higher than that of 5DN. Cell culture studies revealed that 5DN and its colonic metabolites profoundly inhibited the growth of human colon cancer cells by inducing cell cycle arrest, triggering apoptosis and modulating key signaling proteins related to cell proliferation and apoptosis. Importantly, the colonic metabolites, especially M1, showed much stronger effects than those produced by 5DN itself. Overall, our results demonstrated that dietary 5DN significantly inhibited colitis-driven colon carcinogenesis in mice, and this chemopreventive effect was associated with its metabolites in the colon.
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