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.
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Authors | Michele Navarra, Angelo Pietro Femia, Andrea Romagnoli, Katia Tortora, Cristina Luceri, Santa Cirmi, Nadia Ferlazzo, Giovanna Caderni |
Journal | European journal of nutrition
(Eur J Nutr)
Vol. 59
Issue 3
Pg. 885-894
(Apr 2020)
ISSN: 1436-6215 [Electronic] Germany |
PMID | 30919084
(Publication Type: Journal Article)
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Chemical References |
- Flavonoids
- Plant Extracts
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Topics |
- Animals
- Citrus
- Colorectal Neoplasms
(prevention & control)
- Disease Models, Animal
- Flavonoids
(therapeutic use)
- Fruit and Vegetable Juices
- Male
- Models, Genetic
- Plant Extracts
(therapeutic use)
- Rats
- Rats, Inbred F344
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