Anti-Inflammatory Mechanism Involved in Pomegranate-Mediated Prevention of Breast Cancer: the Role of NF-κB and Nrf2 Signaling Pathways.

Animesh Mandal,Anupam Bishayee,Deepak Bhatia

doi:10.3390/nu9050436

Animesh Mandal, Anupam Bishayee + Show 1 more

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https://doi.org/10.3390/nu9050436

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Abstract

Pomegranate (Punica granatum L.), a nutrient-rich unique fruit, has been used for centuries for the prevention and treatment of various inflammation-driven diseases. Based on our previous study, a characterized pomegranate emulsion (PE) exhibited a striking inhibition of dimethylbenz(a)anthracene (DMBA)-initiated rat mammary tumorigenesis via antiproliferative and apoptosis-inducing mechanisms. The objective of the present work is to investigate the anti-inflammatory mechanism of action of PE during DMBA rat mammary carcinogenesis by evaluating the expression of cyclooxygenase-2 (COX-2), heat shock protein 90 (HSP90), nuclear factor-κB (NF-κB) and nuclear factor erythroid 2p45 (NF-E2)-related factor 2 (Nrf2). Mammary tumor samples were harvested from our previous chemopreventive study in which PE (0.2–5.0 g/kg) was found to reduce mammary tumorigenesis in a dose-dependent manner. The expressions of COX-2, HSP90, NF-κB, inhibitory κBα (IκBα) and Nrf2 were detected by immunohistochemical techniques. PE decreased the expression of COX-2 and HSP90, prevented the degradation of IκBα, hindered the translocation of NF-κB from cytosol to nucleus and increased the expression and nuclear translocation of Nrf2 during DMBA-induced mammary tumorigenesis. These findings, together with our previous results, indicate that PE-mediated prevention of DMBA-evoked mammary carcinogenesis may involve anti-inflammatory mechanisms through concurrent but differential regulation of two interrelated molecular pathways, namely NF-κB and Nrf2 signaling.

Highlights

Pomegranate (Punica granatum L.) is a nutrient-rich fruit which represents a reservoir of bioactive phytochemicals with exceptional medicinal values
pomegranate emulsion (PE) at a dose of 0.2 g/kg slightly reduced intratumor COX-2 immunopositivity compared to the DMBA control (Figure 1(Ab))
There was a significant (p < 0.01 or 0.001) inhibition of the percentage of intratumor COX-2-positive cells in animals administered with 1 or 5 g/kg PE compared to the DMBA control, respectively

Summary

Introduction

Pomegranate (Punica granatum L.) is a nutrient-rich fruit which represents a reservoir of bioactive phytochemicals with exceptional medicinal values. Pomegranate fruit has been gaining a widespread reputation as a dietary supplement as well as a functional food due to emerging scientific evidence on potential health benefits, including prevention and/or treatment of cardiovascular ailments, neurological disorders, oncologic diseases, dental problems, inflammation, ulcer, arthritis, microbial. Fractions and phytochemicals from pomegranate fruit, peel, seed and flower demonstrated cytotoxic, antiproliferative, proapoptotic, antiangiogenic, anti-invasive, and antimetastatic properties against estrogen receptor-positive and -negative breast cancer cells [19,20,21,22,23,24,25,26,27,28,29,30,31,32]. Pomegranate seed oil and fermented juice concentrate were found to suppress

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