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

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

Mandal Animesh; Bhatia Deepak; Bishayee Anupam

Nutrients

2017

2017-04

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-kappaB (NF-kappaB) 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-kappaB, inhibitory kappaBalpha (IkappaBalpha) and Nrf2 were detected by immunohistochemical techniques. PE decreased the expression of COX-2 and HSP90, prevented the degradation of IkappaBalpha, hindered the translocation of

Female; Animals; Anti-Inflammatory Agents/*pharmacology; Rats; Gene Expression Regulation; Signal Transduction; Apoptosis/drug effects; anti-inflammatory effects; Anticarcinogenic Agents/pharmacology; breast tumor; COX-2; Cyclooxygenase 2/genetics/metabolism; DMBA; HSP90; HSP90 Heat-Shock Proteins/genetics/metabolism; I-kappa B Kinase/genetics/metabolism; NF-E2-Related Factor 2/genetics/*metabolism; NF-kappa B/genetics/*metabolism; NF-kappaB; Nrf2; Plant Preparations/*pharmacology; Punica granatum; Punicaceae/*chemistry; Pomegranate; Chemoprevention; Dose-Response Relationship; Drug; Neoplastic; Mammary Neoplasms; 10-Dimethyl-1; 9; Neoplastic/drug effects; Cell Transformation; 2-benzanthracene/toxicity; Experimental/*prevention & control; Animal Studies; Breast Neoplasms; Inflammation Mediators; Physical Education and Training; Neoplasms – Prevention and Control

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