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Nutrients 2017, 9(5), 436; doi:10.3390/nu9050436

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

1
Cancer Therapeutics and Chemoprevention Group, Department of Pharmaceutical Sciences, College of Pharmacy, Northeast Ohio Medical University, Rootstown, OH 44272, USA
2
Department of Pharmacogenomics, Bernard J. Dunn School of Pharmacy, Shenandoah University, Ashburn, VA 20147, USA
3
Department of Pharmaceutical Sciences, College of Pharmacy, Larkin University, Miami, FL 33169, USA
*
Author to whom correspondence should be addressed.
Received: 1 February 2017 / Accepted: 5 April 2017 / Published: 28 April 2017
(This article belongs to the Special Issue Nutrients, Infectious and Inflammatory Diseases)
View Full-Text   |   Download PDF [4666 KB, uploaded 28 April 2017]   |  

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. View Full-Text
Keywords: anti-inflammatory effects; breast tumor; COX-2; DMBA; HSP90; NF-κB; Nrf2; Punica granatum anti-inflammatory effects; breast tumor; COX-2; DMBA; HSP90; NF-κB; Nrf2; Punica granatum
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Mandal, A.; Bhatia, D.; Bishayee, A. Anti-Inflammatory Mechanism Involved in Pomegranate-Mediated Prevention of Breast Cancer: the Role of NF-κB and Nrf2 Signaling Pathways. Nutrients 2017, 9, 436.

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