Eleostearic Acid Inhibits Breast Cancer Proliferation by Means of an Oxidation-Dependent Mechanism
Eleostearic Acid Inhibits Breast Cancer Proliferation by Means of an Oxidation-Dependent Mechanism
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DOI：
10.1158/1940-6207.capr-09-0088
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发表时间：
2009-10-01
影响因子：
3.3
通讯作者：
Cleary, Margot P.
中科院分区：
文献类型：
--
作者：
Grossmann, Michael E.;Mizuno, Nancy K.;Cleary, Margot P.
桐酸（alpha-ESA）是一种共轭亚麻酸，占苦瓜籽油的60%。先前的研究发现，苦瓜的水提取物能够抑制乳腺癌。在这里，我们研究了α-ESA对雌激素受体（ER）阴性MDA-MB-231（MDA-wt）和ER阳性MDA-ER α 7人乳腺癌细胞的影响。我们发现，α-ESA抑制MDA-wt和MDA-ER α 7细胞的增殖，而共轭亚油酸在20至80 μ mol/L浓度下具有相对较弱的抗增殖活性。我们还发现，α-ESA（40 μ mol/L）处理导致两种细胞系的凋亡在70%至90%的范围内，而共轭亚油酸（40 μ mol/L）导致只有5%至10%的凋亡，类似于对照未处理细胞的结果。添加α-ESA还引起线粒体膜电位的损失和易位的凋亡诱导因子以及核酸内切酶G从线粒体到细胞核。此外，α-ESA在细胞周期中引起G（2）-M阻滞。我们还研究了脂质过氧化在α-ESA的抑制作用中发挥作用的可能性。我们发现，当在抗氧化剂α-生育三烯酚（20 μ mol/L）存在下用α-ESA处理乳腺癌细胞时，α-ESA的生长抑制和凋亡作用丧失。AMP活化的蛋白激酶抑制剂（Dorsomorphin）也能够部分消除α-ESA的作用，而半胱天冬酶抑制剂（BOC-D-FMK）则不能。这些结果表明，α-ESA可以通过氧化依赖性机制阻断乳腺癌细胞增殖并诱导细胞凋亡。
Eleostearic acid (alpha-ESA) is a conjugated linolenic acid that makes up similar to 60% of Momordica charantia (bitter melon) seed oil. Prior work found that water extract from bitter melon was able to inhibit breast cancer. Here, we investigated effects of alpha-ESA on both estrogen receptor (ER)-negative MDA-MB-231 (MDA-wt) and ER-positive MDA-ER alpha 7 human breast cancer cells. We found that a-ESA inhibited proliferation of both MDA-wt and MDA-ER alpha 7 cells, whereas conjugated linoleic acid had comparatively weak antiproliferative activity at 20 to 80 mu mol/L concentrations. We also found that alpha-ESA (40 mu mol/L) treatment led to apoptosis in the range of 70% to 90% for both cell lines, whereas conjugated linoleic acid (40 mu mol/L) resulted in only 5% to 10% apoptosis, similar to results for control untreated cells. Addition of alpha-ESA also caused loss of mitochondrial membrane potential and translocation of apoptosis-inducing factor as well as endonuclease G from the mitochondria to the nucleus. Additionally, alpha-ESA caused a G(2)-M block in the cell cycle. We also investigated the potential for lipid peroxidation to play a role in the inhibitory action of alpha-ESA. We found that when the breast cancer cells were treated with alpha-ESA in the presence of the antioxidant alpha-tocotrienol (20 mu mol/L), the growth inhibition and apoptosis effects of alpha-ESA were lost. An AMP-activated protein kinase inhibitor (Dorsomorphin) was also able to partially abrogate the effects of alpha-ESA, whereas a caspase inhibitor (BOC-D-FMK) did not. These results illustrate that alpha-ESA can block breast cancer cell proliferation and induce apoptosis through a mechanism that may be oxidation dependent.