Skip to main content
Top
Published in: European Journal of Nutrition 3/2020

01-04-2020 | Colorectal Cancer | Original Contribution

A flavonoid-rich extract from bergamot juice prevents carcinogenesis in a genetic model of colorectal cancer, the Pirc rat (F344/NTac-Apcam1137)

Authors: Michele Navarra, Angelo Pietro Femia, Andrea Romagnoli, Katia Tortora, Cristina Luceri, Santa Cirmi, Nadia Ferlazzo, Giovanna Caderni

Published in: European Journal of Nutrition | Issue 3/2020

Login to get access

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.
Literature
7.
go back to reference Visalli G, Ferlazzo N, Cirmi S, Campiglia P, Gangemi S, Pietro AD, Calapai G, Navarra M (2014) Bergamot juice extract inhibits proliferation by inducing apoptosis in human colon cancer cells. Anticancer Agents Med Chem 14(10):1402–1413CrossRef Visalli G, Ferlazzo N, Cirmi S, Campiglia P, Gangemi S, Pietro AD, Calapai G, Navarra M (2014) Bergamot juice extract inhibits proliferation by inducing apoptosis in human colon cancer cells. Anticancer Agents Med Chem 14(10):1402–1413CrossRef
14.
17.
go back to reference Ferlazzo N, Visalli G, Smeriglio A, Cirmi S, Lombardo GE, Campiglia P, Di Pietro A, Navarra M (2015) Flavonoid fraction of orange and bergamot juices protect human lung epithelial cells from hydrogen peroxide-induced oxidative stress. Evid Based Complement Altern Med 2015:957031. https://doi.org/10.1155/2015/957031 CrossRef Ferlazzo N, Visalli G, Smeriglio A, Cirmi S, Lombardo GE, Campiglia P, Di Pietro A, Navarra M (2015) Flavonoid fraction of orange and bergamot juices protect human lung epithelial cells from hydrogen peroxide-induced oxidative stress. Evid Based Complement Altern Med 2015:957031. https://​doi.​org/​10.​1155/​2015/​957031 CrossRef
22.
go back to reference Caderni G, De Filippo C, Luceri C, Salvadori M, Giannini A, Biggeri A, Remy S, Cheynier V, Dolara P (2000) Effects of black tea, green tea and wine extracts on intestinal carcinogenesis induced by azoxymethane in F344 rats. Carcinogenesis 21(11):1965–1969CrossRef Caderni G, De Filippo C, Luceri C, Salvadori M, Giannini A, Biggeri A, Remy S, Cheynier V, Dolara P (2000) Effects of black tea, green tea and wine extracts on intestinal carcinogenesis induced by azoxymethane in F344 rats. Carcinogenesis 21(11):1965–1969CrossRef
23.
go back to reference Caderni G, Femia AP, Giannini A, Favuzza A, Luceri C, Salvadori M, Dolara P (2003) Identification of mucin-depleted foci in the unsectioned colon of azoxymethane-treated rats: correlation with carcinogenesis. Cancer Res 63(10):2388–2392PubMed Caderni G, Femia AP, Giannini A, Favuzza A, Luceri C, Salvadori M, Dolara P (2003) Identification of mucin-depleted foci in the unsectioned colon of azoxymethane-treated rats: correlation with carcinogenesis. Cancer Res 63(10):2388–2392PubMed
24.
go back to reference Femia AP, Luceri C, Bianchini F, Salvadori M, Salvianti F, Pinzani P, Dolara P, Calorini L, Caderni G (2012) Marie Menard apples with high polyphenol content and a low-fat diet reduce 1,2-dimethylhydrazine-induced colon carcinogenesis in rats: effects on inflammation and apoptosis. Mol Nutr Food Res 56(8):1353–1357. https://doi.org/10.1002/mnfr.201200122 CrossRefPubMed Femia AP, Luceri C, Bianchini F, Salvadori M, Salvianti F, Pinzani P, Dolara P, Calorini L, Caderni G (2012) Marie Menard apples with high polyphenol content and a low-fat diet reduce 1,2-dimethylhydrazine-induced colon carcinogenesis in rats: effects on inflammation and apoptosis. Mol Nutr Food Res 56(8):1353–1357. https://​doi.​org/​10.​1002/​mnfr.​201200122 CrossRefPubMed
39.
go back to reference Femia AP, Dolara P, Luceri C, Salvadori M, Caderni G (2009) Mucin-depleted foci show strong activation of inflammatory markers in 1,2-dimethylhydrazine-induced carcinogenesis and are promoted by the inflammatory agent sodium dextran sulfate. Int J Cancer 125(3):541–547. https://doi.org/10.1002/ijc.24417 CrossRefPubMed Femia AP, Dolara P, Luceri C, Salvadori M, Caderni G (2009) Mucin-depleted foci show strong activation of inflammatory markers in 1,2-dimethylhydrazine-induced carcinogenesis and are promoted by the inflammatory agent sodium dextran sulfate. Int J Cancer 125(3):541–547. https://​doi.​org/​10.​1002/​ijc.​24417 CrossRefPubMed
46.
go back to reference Sun SY, Hail N Jr, Lotan R (2004) Apoptosis as a novel target for cancer chemoprevention. J Natl Cancer Inst 96(9):662–672CrossRef Sun SY, Hail N Jr, Lotan R (2004) Apoptosis as a novel target for cancer chemoprevention. J Natl Cancer Inst 96(9):662–672CrossRef
Metadata
Title
A flavonoid-rich extract from bergamot juice prevents carcinogenesis in a genetic model of colorectal cancer, the Pirc rat (F344/NTac-Apcam1137)
Authors
Michele Navarra
Angelo Pietro Femia
Andrea Romagnoli
Katia Tortora
Cristina Luceri
Santa Cirmi
Nadia Ferlazzo
Giovanna Caderni
Publication date
01-04-2020
Publisher
Springer Berlin Heidelberg
Published in
European Journal of Nutrition / Issue 3/2020
Print ISSN: 1436-6207
Electronic ISSN: 1436-6215
DOI
https://doi.org/10.1007/s00394-019-01948-z

Other articles of this Issue 3/2020

European Journal of Nutrition 3/2020 Go to the issue