N-3 poly-unsaturated fatty acids shift estrogen signaling to inhibit human breast cancer cell growth.
N-3 poly-unsaturated fatty acids shift estrogen signaling to inhibit human breast cancer cell growth.
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DOI：
10.1371/journal.pone.0052838
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Yu J
中科院分区：
文献类型：
--
作者：
Cao W;Ma Z;Rasenick MM;Yeh S;Yu J
尽管已有证据表明n-3多不饱和脂肪酸(n-3 PUFA)对细胞信号转导有调节作用，但n-3多不饱和脂肪酸处理是否对雌激素信号转导有调节作用尚不清楚。目前的研究表明，二十二碳六烯酸(DHA，C22：6)和二十碳五烯酸(EPA，C20：5)使雌激素对人乳腺癌MCF-7和T47D细胞的促存活和促增殖作用转变为促凋亡作用。17-多不饱和脂肪酸(17-β-estadiol，E_2)可增强n-3PUFAs对BCA细胞生长的抑制作用。DHA或EPA在MCF-7细胞中与E2(10 NM)联合作用的IC50降低(从仅DHA的173微米降至DHA+E2的113微米，EPA单独的IC50从187微米降至130微米)。E_2还可促进n-3PUFA处理的BCA细胞的凋亡。相反，在用硬脂酸(SA，C18：0)处理的细胞和未用脂肪酸处理的细胞中，E2促进了乳腺癌细胞的生长。经典的(核)雌激素受体可能不参与雌激素对n-3多不饱和脂肪酸诱导的BCA细胞的促凋亡作用，因为ERα激动剂不能诱导，ERα基因敲除也不能阻断E2促凋亡的作用。随后的研究发现，G蛋白偶联雌激素受体1(GPER1)可能介导了雌激素的促凋亡作用。N-3多不饱和脂肪酸通过增加GPER1-cAMP-PKA信号反应，钝化EGFR、Erk1/2和AKT活性，启动雌激素促凋亡信号转导。这些发现不仅可能为将n-3PUFAs的生物学效应与雌激素在乳腺癌细胞中的促凋亡信号联系起来提供证据，而且也为n-3PUFAs在BCA治疗中的潜在应用提供了新的见解。
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 β-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 µM for DHA only to 113 µM for DHA+E2, and from 187 µm for EPA only to 130 µm 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 ERα agonist failed to elicit, and ERα 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.
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影响因子：
11.2
作者：
Ariazi EA;Brailoiu E;Yerrum S;Shupp HA;Slifker MJ;Cunliffe HE;Black MA;Donato AL;Arterburn JB;Oprea TI;Prossnitz ER;Dun NJ;Jordan VC
通讯作者：
Jordan VC
影响因子：
4.5
作者：
Corsetto PA;Montorfano G;Zava S;Jovenitti IE;Cremona A;Berra B;Rizzo AM
通讯作者：
Rizzo AM
DOI：
10.1073/pnas.91.18.8517
发表时间：
1994-08-30
影响因子：
11.1
作者：
ARONICA, SM;KRAUS, WL;KATZENELLENBOGEN, BS
通讯作者：
KATZENELLENBOGEN, BS
影响因子：
64.5
作者：
KATO, JY;MATSUOKA, M;SHERR, CJ
通讯作者：
SHERR, CJ
DOI：
10.1073/pnas.1115188108
发表时间：
2011-11-22
影响因子：
11.1
作者：
Ariazi, Eric A.;Cunliffe, Heather E.;Jordan, V. Craig
通讯作者：
Jordan, V. Craig