Michele Navarra1, Angelo Pietro Femia2, Andrea Romagnoli2, Katia Tortora2, Cristina Luceri2, Santa Cirmi3,4, Nadia Ferlazzo3, Giovanna Caderni2. 1. Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Messina, Italy. mnavarra@unime.it. 2. Section of Pharmacology and Toxicology, NEUROFARBA Department, University of Florence, Florence, Italy. 3. Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Messina, Italy. 4. Fondazione "Prof. Antonio Imbesi", Messina, Italy.
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.
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 lesionsmucin-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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