Dietary polyphenols suppress elevated levels of proinflammatory mediators and aromatase in the mammary gland of obese mice
Authors: Priya Bhardwaj
Levy Kopelovich
Dilip Giri
Baoheng Du
Xi Kathy Zhou
Erika Sue
Andrew J Dannenberg
Kotha Subbaramaiah
Clifford A Hudis
Journal: Cancer Prevention Research (2013)
Discipline: CLINICAL MEDICINE
Keywords: postmenopausal women; obesity; hormone receptor-positive breast cancer; estrogen; aromatization
Affiliations: Department of Medicine, Weill Cornell Medical College, 525 East 68th St, Room F-206, New York, New York 10065, USA. 

Abstract:  In postmenopausal women, obesity is a risk factor for the development of hormone receptor-positive breast cancer driven by estrogen. After menopause, aromatization of androgen precursors in adipose tissue is a major synthetic source of estrogen. Recently, in mouse models and women, we identified an obesity-inflammation-aromatase axis. This obesity-induced inflammation is characterized by crown-like structures (CLS) consisting of dead adipocytes encircled by macrophages in breast white adipose tissue. CLS occur in association with NF-κB activation, elevated levels of proinflammatory mediators, and increased aromatase expression. Saturated fatty acids released from adipocytes have been linked to obesity-related white adipose tissue inflammation. Here we found that stearic acid, a prototypic saturated fatty acid, stimulated Akt-dependent activation of NF-κB resulting in increased levels of proinflammatory mediators [TNF-α, interleukin (IL)-1β, COX-2] in macrophages leading, in turn, to the induction of aromatase. Several polyphenols (resveratrol, curcumin, epigallocatechin gallate) blocked these inductive effects of stearic acid. Zyflamend, a widely used polyherbal preparation that contains numerous polyphenols, possessed similar suppressive effects. In a mouse model of obesity, treatment with Zyflamend suppressed levels of phospho-Akt, NF-κB binding activity, proinflammatory mediators, and aromatase in the mammary gland. Collectively, these results suggest that targeting the activation of NF-κB is a promising approach for reducing levels of proinflammatory mediators and aromatase in inflamed mouse mammary tissue. Further investigation in obese women is warranted. 

Retracted: Yes

PubPeer comments:
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 https: retractionwatch.com 2020 01 03 prominent-cancer-researcher-loses-eight-papers-making-11 , 
 Retracted [2 June 2022] .  This article (1) has been retracted at the request of the authors. There was evidence of data falsification or fabrication found in four figures. Suspicious duplications of band images were found in Figs. 1D, 2D, 3D, and 6C. A copy of this Retraction Notice was sent to the last known e-mail addresses for the 9 authors. Seven authors (Kotha Subbaramaiah, Priya Bhardwaj, Clifford A. Hudis, Dilip Giri, Levy Kopelovich, Xi Kathy Zhou, and Andrew J. Dannenberg) agreed to the retraction; two authors (Baoheng Du and Erika Sue) did not respond. The authors apologize to the scientific community and deeply regret any inconveniences or challenges resulting from the publication and subsequent retraction of this article. , 
 https: retractionwatch.com 2022 06 03 former-weill-cornell-cancer-researcher-up-to-20-retractions-investigations-findings-are-with-feds ,