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- Title
A flavonoid-rich extract from bergamot juice prevents carcinogenesis in a genetic model of colorectal cancer, the Pirc rat (F344/NTac-Apcam1137).
- Authors
Navarra, Michele; Femia, Angelo Pietro; Romagnoli, Andrea; Tortora, Katia; Luceri, Cristina; Cirmi, Santa; Ferlazzo, Nadia; Caderni, Giovanna
- Abstract
Purpose: To determine the potential of a flavonoid-rich extract from bergamot juice (BJe) to prevent colorectal carcinogenesis (CRC) in vivo. Main methods: Pirc rats (F344/NTac-Apcam1137), mutated in Apc, the key gene in CRC, were treated with two different doses of BJe (35 mg/kg or 70 mg/kg body weight, respectively) mixed in the diet for 12 weeks. Then, the entire intestine was surgically removed and dissected for histological, immunohistochemical and molecular analyses. Results: Rats treated with BJe showed a significant dose-related reduction in the colon preneoplastic lesions mucin-depleted foci (MDF). Colon and small intestinal tumours were also significantly reduced in rats supplemented with 70 mg/kg of BJe. To elucidate the involved mechanisms, markers of inflammation and apoptosis were determined. Compared to controls, colon tumours from BJe 70 mg/kg-supplemented rats showed a significant down-regulation of inflammation-related genes (COX-2, iNOS, IL-1β, IL-6 and IL-10 and Arginase 1). Moreover, in colon tumours from rats fed with 70 mg/kg BJe, apoptosis was significantly higher than in controls. Up-regulation of p53 and down-regulation of survivin and p21 genes was also observed. Conclusions: These data indicate a strong chemopreventive activity of BJe that, at least in part, is due to its pro-apoptotic and anti-inflammatory actions. This effect could be exploited as a strategy to prevent CRC in high-risk patients.
- Subjects
FRUIT juices -- Therapeutic use; INFLAMMATION prevention; CARCINOGENESIS; ANIMAL experimentation; ANTINEOPLASTIC agents; APOPTOSIS; BIOLOGICAL models; CELL lines; CHEMOPREVENTION; CITRUS; COLON tumors; DOSE-effect relationship in pharmacology; FLAVONOIDS; GENE expression; HISTOLOGICAL techniques; IMMUNOHISTOCHEMISTRY; PRECANCEROUS conditions; RATS; RECTUM tumors; PLANT extracts; TREATMENT effectiveness; PHARMACODYNAMICS
- Publication
European Journal of Nutrition, 2020, Vol 59, Issue 3, p885
- ISSN
1436-6207
- Publication type
Article
- DOI
10.1007/s00394-019-01948-z