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Cancer Prev Res (Phila). 2013 Sep;6(9):886-97. doi: 10.1158/1940-6207.CAPR-13-0140. Epub 2013 Jul 23.

Dietary polyphenols suppress elevated levels of proinflammatory mediators and aromatase in the mammary gland of obese mice.

Author information

1
Department of Medicine, Weill Cornell Medical College, 525 East 68th St, Room F-206, New York, New York 10065, USA. ksubba@med.cornell.edu

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.

PMID:
23880231
PMCID:
PMC3767430
DOI:
10.1158/1940-6207.CAPR-13-0140
[Indexed for MEDLINE]
Free PMC Article

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