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R.B. · 11-18-2013, 02:54 PM

Thing are rarely simple, and still much is unknown; the mysteries of estrogen !

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

http://www.plosone.org/article/info%...l.pone.0052838

WenQing Cao, ZhiFan Ma, Mark M. Rasenick, ShuYan Yeh, JiangZhou Yu

"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."

"Introduction

Fish oil dietary supplements have become increasingly popular. They are consumed for a variety of ailments as well as for promotion of general health. Population and preclinical studies have suggested that n-3 PUFAs inhibit BCa growth and improve treatment outcomes [1]. Accumulating evidence states that n-3 PUFAs may exert an antitumor action by altering lipid composition of the plasma membrane, which may affect the physical and chemical properties of lipid rafts, consequently, affecting localization of and interactions among signaling components in the microdomains of cell membrane [2]–[4]. Recent studies in breast cancer cells also found that, n-3 PUFA could incorporate different components of the cell membrane to remodel membrane architecture [5], [6]. These suggested a potential mechanism underlying n-3 PUFA anti-cancer effect. N-3 PUFA treatment decreases EGFR signaling [7], and down-regulates CXCR4 signaling in MDA-MB-231 cells [8], which might play the important roles in the anti-BCa effect of n-3 PUFAs. While E2 signaling is crucial for BCa tumorigenesis and progression, fewer studies have addressed how n-3 PUFAs affect E2 signaling and biologic function in BCa cells. It is noteworthy that in the animal studies on chemo-preventive properties of n-3 PUFAs, estrogen does not override the inhibitory effect of high n-3 PUFA diet on BCa growth [9], implying that n-3 PUFAs might abrogate/reduce/reverse the pro-proliferative effect of estrogen.

Estrogen, a mitogen, stimulates cell proliferation and prevents cell death in many different cell types, and is an important risk factor for BCa development [10]. Anti-estrogen therapies have been widely employed to treat hormone dependent BCa. However, laboratory studies have suggested that estrogen stimulates the apoptosis in long-term estrogen deprivation of MCF-7 BCa cells, and switches from being a mitogenic agent to inhibiting growth and inducing apoptosis [11]–[13]. Two potential mechanisms underlying this paradoxical effect of estrogen have been suggested in the studies that can be triggered either through the extrinsic death receptor pathway [12] or via the intrinsic pathway of mitochondrial disruption and release of cytochrome C [11]. Nevertheless, it is not clear how estrogen might promote BCa cell apoptosis.

Based on the above scientific findings, we propose that n-3 PUFAs alter estrogen signaling cascades in BCa cells, and initiate/augment the inhibitory effect of E2 (or compounds binding to membrane E2 receptors) on breast cancer. In this study, we first found that n-3 PUFA treatment initiated the inhibitory effect of E2 on MCF-7 and T47D BCa cell growth, and increased cell apoptosis. While these effects of estrogen were independent of the classical estrogen receptors, ERα or ERβ, they required the presence of the estrogen-sensitive G protein coupled receptor (GPCR), GPER1. Data from this study could lead to novel insights into the usefulness of n-3 PUFAs in the treatment of BCa."

11-18-2013, 02:54 PM	#416
R.B. Senior Member Join Date: Mar 2006 Posts: 1,843	Re: The traditional diet of Greece and cancer. Thing are rarely simple, and still much is unknown; the mysteries of estrogen ! N-3 Poly-Unsaturated Fatty Acids Shift Estrogen Signaling to Inhibit Human Breast Cancer Cell Growth http://www.plosone.org/article/info%...l.pone.0052838 WenQing Cao, ZhiFan Ma, Mark M. Rasenick, ShuYan Yeh, JiangZhou Yu "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." "Introduction Fish oil dietary supplements have become increasingly popular. They are consumed for a variety of ailments as well as for promotion of general health. Population and preclinical studies have suggested that n-3 PUFAs inhibit BCa growth and improve treatment outcomes [1]. Accumulating evidence states that n-3 PUFAs may exert an antitumor action by altering lipid composition of the plasma membrane, which may affect the physical and chemical properties of lipid rafts, consequently, affecting localization of and interactions among signaling components in the microdomains of cell membrane [2]–[4]. Recent studies in breast cancer cells also found that, n-3 PUFA could incorporate different components of the cell membrane to remodel membrane architecture [5], [6]. These suggested a potential mechanism underlying n-3 PUFA anti-cancer effect. N-3 PUFA treatment decreases EGFR signaling [7], and down-regulates CXCR4 signaling in MDA-MB-231 cells [8], which might play the important roles in the anti-BCa effect of n-3 PUFAs. While E2 signaling is crucial for BCa tumorigenesis and progression, fewer studies have addressed how n-3 PUFAs affect E2 signaling and biologic function in BCa cells. It is noteworthy that in the animal studies on chemo-preventive properties of n-3 PUFAs, estrogen does not override the inhibitory effect of high n-3 PUFA diet on BCa growth [9], implying that n-3 PUFAs might abrogate/reduce/reverse the pro-proliferative effect of estrogen. Estrogen, a mitogen, stimulates cell proliferation and prevents cell death in many different cell types, and is an important risk factor for BCa development [10]. Anti-estrogen therapies have been widely employed to treat hormone dependent BCa. However, laboratory studies have suggested that estrogen stimulates the apoptosis in long-term estrogen deprivation of MCF-7 BCa cells, and switches from being a mitogenic agent to inhibiting growth and inducing apoptosis [11]–[13]. Two potential mechanisms underlying this paradoxical effect of estrogen have been suggested in the studies that can be triggered either through the extrinsic death receptor pathway [12] or via the intrinsic pathway of mitochondrial disruption and release of cytochrome C [11]. Nevertheless, it is not clear how estrogen might promote BCa cell apoptosis. Based on the above scientific findings, we propose that n-3 PUFAs alter estrogen signaling cascades in BCa cells, and initiate/augment the inhibitory effect of E2 (or compounds binding to membrane E2 receptors) on breast cancer. In this study, we first found that n-3 PUFA treatment initiated the inhibitory effect of E2 on MCF-7 and T47D BCa cell growth, and increased cell apoptosis. While these effects of estrogen were independent of the classical estrogen receptors, ERα or ERβ, they required the presence of the estrogen-sensitive G protein coupled receptor (GPCR), GPER1. Data from this study could lead to novel insights into the usefulness of n-3 PUFAs in the treatment of BCa." Last edited by R.B.; 11-18-2013 at 03:19 PM..