POMEGRANATE BY-PRODUCTS AS A SOURCE OF POLYPHENOLS AND FIBERS: POTENTIAL COLORECTAL CANCER CHEMOPREVENTIVE ACTIVITY OF A MESOCARP DECOCTION

Introduction: We investigated the possibility of employing a pomegranate mesocarp decoction (PMD), a fruit by-product rich in punicalagin and fibers, for colorectal cancer (CRC) prevention. Materials and Methods: We have assessed effects and mechanisms of action of PMD in vivo administering PMD for six weeks to one-month old Pirc male rats, bearing an Apc gene mutation (1), in vitro on HT-29 cell line and ex vivo on adenoma (AD) and normal mucosa (NM) of Pirc rats, testing the colonic PMD metabolites urolithin-A (u-A) and sodium butyrate (SB) alone or in combination (USB). Results: PMD reduced the number of Multiple Depleted Foci (MDFs), a CRC biomarker (2), in PMD-treated rats (-30%, p< 0.05 compared to controls), and increased apoptosis in MDFs. In HT-29 cells and in ADs and NMs, USB (u-A 25 µM plus SB 2.5 mM) caused a significant reduction in COX-2 expression compared to untreated controls (-74.5% in HT-29 and -76.5%, -69.02% in AD and NM respectively) and a strong increase in C-CASP-3 expression in HT-29 cells (10 times), in AD and NM (+74% and +69% respectively). Conclusion: PMD appears to act at early CRC phases (MDF), probably through a pro-apoptotic and anti-inflammatory action of u-A and SB.