Dietary polyphenols suppress elevated levels of proin flammatory mediators and aromatase in the mammary gland of obese mice Journal Article
| Authors: | Subbaramaiah, K.; Sue, E.; Bhardwaj, P.; Du, B.; Hudis, C. A.; Giri, D.; Kopelovich, L.; Zhou, X. K.; Dannenberg, A. J. |
| Article Title: | Dietary polyphenols suppress elevated levels of proin flammatory mediators and aromatase in the mammary gland of obese mice |
| 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 Aktdependent activation of NF-κB resulting in increased levels of proinflammatory mediators [TNF-&alpha, 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 ©2013 AACR. |
| Journal Title: | Cancer Prevention Research |
| Volume: | 6 |
| Issue: | 9 |
| ISSN: | 1940-6207 |
| Publisher: | American Association for Cancer Research |
| Date Published: | 2013-09-01 |
| Start Page: | 886 |
| End Page: | 897 |
| Language: | English |
| DOI: | 10.1158/1940-6207.capr-13-0140 |
| PROVIDER: | scopus |
| PMCID: | PMC3767430 |
| PUBMED: | 23880231 |
| DOI/URL: | |
| Notes: | "Export Date: 1 October 2013" - "Source: Scopus" |
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