INDIGO Home University of Illinois at Urbana-Champaign logo uic building uic pavilion uic student center

N-3 Poly-Unsaturated Fatty Acids Shift Estrogen Signaling to Inhibit Human Breast Cancer Cell Growth

Show full item record

Bookmark or cite this item: http://hdl.handle.net/10027/10836

Files in this item

File Description Format
PDF journal.pone.0052838.pdf (1MB) Main Article PDF
Title: N-3 Poly-Unsaturated Fatty Acids Shift Estrogen Signaling to Inhibit Human Breast Cancer Cell Growth
Author(s): Cao, WenQing; Ma, ZhiFan; Rasenick, Mark M.; Yeh, ShuYan; Yu, JiangZhou
Subject(s): apoptosis omega-3 fatty acids cell line tumor
Abstract: Although evidence has shown the regulating effect of n-3 poly-unsaturated fatty acid (n-3 PUFA) on cell signaling transduction, it remains unknown whether n-3 PUFA treatment modulates estrogen signaling. The current study showed that docosahexaenoic acid (DHA, C22:6), eicosapentaenoic acid (EPA, C20:5) shifted the pro-survival and proliferative effect of estrogen to a pro-apoptotic effect in human breast cancer (BCa) MCF-7 and T47D cells. 17 beta-estradiol (E2) enhanced the inhibitory effect of n-3 PUFAs on BCa cell growth. The IC50 of DHA or EPA in MCF-7 cells decreased when combined with E2 (10 nM) treatment (from 173 mu M for DHA only to 113 mu M for DHA+E2, and from 187 mu m for EPA only to 130 mu m for EPA+E2). E2 also augmented apoptosis in n-3 PUFA-treated BCa cells. In contrast, in cells treated with stearic acid (SA, C18:0) as well as cells not treated with fatty acid, E2 promoted breast cancer cell growth. Classical (nuclear) estrogen receptors may not be involved in the pro-apoptotic effects of E2 on the n-3 PUFA-treated BCa cells because ER alpha agonist failed to elicit, and ER alpha knockdown failed to block E2 pro-apoptotic effects. Subsequent studies reveal that G protein coupled estrogen receptor 1 (GPER1) may mediate the pro-apoptotic effect of estrogen. N-3 PUFA treatment initiated the pro-apoptotic signaling of estrogen by increasing GPER1-cAMP-PKA signaling response, and blunting EGFR, Erk 1/2, and AKT activity. These findings may not only provide the evidence to link n-3 PUFAs biologic effects and the pro- apoptotic signaling of estrogen in breast cancer cells, but also shed new insight into the potential application of n-3 PUFAs in BCa treatment.
Issue Date: 2012-12
Publisher: Public Library of Science
Citation Info: Cao W, Ma Z, Rasenick MM, Yeh S, Yu J (2012) N-3 Poly-Unsaturated Fatty Acids Shift Estrogen Signaling to Inhibit Human Breast Cancer Cell Growth. PLoS ONE 7(12): e52838. doi:10.1371/journal.pone.0052838
Type: Article
Description: © 2012 Cao et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. This is a copy of an article published in the PLoS ONE © 2012 Public Library of Science.
URI: http://hdl.handle.net/10027/10836
ISSN: 1932-6203
Sponsor: Funding for this project was provided by Department of Pathology and Lab Medicine, University of Rochester Medical Center, Rochester, NY, USA.
Date Available in INDIGO: 2013-12-06
 

This item appears in the following Collection(s)

Show full item record

Statistics

Country Code Views
United States of America 413
China 109
Germany 32
Ukraine 25
Japan 12

Browse

My Account

Information

Access Key