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Abstract Title:

Pomegranate By-Products in Colorectal Cancer Chemoprevention: Effects in Apc-Mutated Pirc Rats and Mechanistic Studies in vitro and ex vivo.

Abstract Source:

Mol Nutr Food Res. 2017 Sep 25. Epub 2017 Sep 25. PMID: 28948694

Abstract Author(s):

Katia Tortora, Angelo Pietro Femia, Andrea Romagnoli, Irene Sineo, Mohamad Khatib, Nadia Mulinacci, Lisa Giovannelli, Giovanna Caderni

Article Affiliation:

Katia Tortora

Abstract:

SCOPE: To investigate the effect of pomegranate mesocarp, a polyphenol-rich by-product of juice production, in colorectal cancer (CRC) chemoprevention.

METHODS AND RESULTS: A mesocarp decoction (PMD) was administered for 6 weeks in the diet to Pirc rats, mutated in Apc, a key-gene in CRC. Mucin Depleted Foci (MDFs), as CRC biomarkers, were reduced in PMD-fed rats compared to Controls (MDF/colon: 34±4 vs 47±3, P = 0.02). Apoptosis in MDFs from PMD-treated rats was increased compared to Controls (2.5±0.2 vs 1.6±0.2, P<0.01). To elucidate the involved mechanisms, two colon-relevant metabolites of the polyphenolic and fiber PMD components, urolithin-A (u-A) and sodium butyrate (SB), were tested alone or in combination in vitro (colon cancer cells), and ex vivo in adenoma (AD) and normal mucosa (NM) from Pirc rats. U-A 25μM plus SB 2.5 mM (USB) caused a significant reduction in COX-2 protein expression compared to untreated controls (about -70% in cancer cell cultures, AD, NM), and a strong increase in C-CASP-3 expression in cells (about 10 times), in AD and NM (+74% and +69%).

CONCLUSION: These data indicate a chemopreventive activity of PMD due, at least in part, to pro-apoptotic and anti-inflammatory action of its metabolites, that could be exploited in high-risk patients. This article is protected by copyright. All rights reserved.

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