Climacteric the Journal of the International Menopause Society, 2014, 17(4):385-92.

Phytoestrogens induce apoptosis through a mitochondria/caspase pathway in human breast cancer cells

F-P Chen, M-H Chien

Department of Obstetrics and Gynecology, Keelung Chang Gung Memorial Hospital, and Chang Gung University , Taiwan

OBJECTIVE:

To explore the effect and pathway of phytoestrogens on the growth of breast cancer cell line MCF-7.

METHODS:

MCF-7 cells (human estrogen receptor-positive and progesterone receptor-positive breast cancer cells) were cultured in serum-free medium for 24 h and then treated with genistein, resveratrol, and quercetin (10(-10)-10(-4) mol/l). After further incubation for 24, 48, 72, and 92 h, the cells were harvested and extracted for 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. According to the above results, the proteins involving proliferative and apoptotic pathways were evaluated by Western blot analysis.

RESULTS:

Genistein, resveratrol, and quercetin significantly inhibited cellular proliferation in a dose- and time-dependent manner. Significantly elevated caspase-3 activity was noted after treatment with genistein (10(-9)-10(-7) mol/l), as well as with resveratrol and quercetin (10(-9)-10(-5) mol/l). Significant reduction of PI3K and AKT protein and significant increase of Fas ligand, Fas-associated protein with death domain, cytochrome C, truncated Bid, caspase-9, and caspase-3 were all noted after genistein, resveratrol, and quercetin treatment. 17β-Estradiol induced completely opposite results. Estrogen receptor (ER) α expression was significantly increased with 17β-estradiol, whereas ERβ expression was significantly elevated in the cultures with genistein, resveratrol, and quercetin.

CONCLUSIONS:

These data demonstrate that genistein, resveratrol, and quercetin have antiproliferative effects on breast cancer cells. Their induction of apoptosis involves the activation of both the intrinsic and extrinsic apoptotic pathways, which may be related to the differential affinity to ERα and ERβ. Whether phytoestrogens have similar effects on normal breast cells remains to be examined.

英国《更年期︰ 国际更年期学会会刊》，2014年8月

在人体乳腺癌细胞中植物雌激素通过一种线粒体/半胱氨酸蛋白酶途径诱导细胞凋亡

陈F-P，简M-H

中国台湾长庚大学基隆长庚医院妇产科

目的︰

为了探究植物雌激素对乳腺癌细胞 MCF-7生长的影响和途径。

方法︰

MCF-7 细胞 （人体雌激素受体阳性和孕酮受体阳性的乳腺癌细胞）被放置在无血清培养基中 24 小时进行培养，然后用金雀异黄素、 白藜芦醇和槲皮素 (10^-10-10^-4mol/L)处理。在进一步孵化 24、 48、 72 和 92 h之后， 用MTT法检测得到的细胞。根据上述结果，通过免疫印迹分析评定涉及细胞增殖和凋亡通路的蛋白质。

结果︰

金雀异黄素、 白藜芦醇和槲皮素明显抑制细胞的增殖，以剂量和时间依赖的方式。在用金雀异黄素 (10^-9-10^-7 mol/L)，以及白藜芦醇和槲皮素 (10^-9-10^-5 mol/L) 治疗后，半胱氨酸蛋白酶-3 的活性显著提高。在用金雀异黄素、 白藜芦醇和槲皮素处理后发现，PI3K 和 AKT 蛋白显著减少并且Fas 配体，Fas 相关凋亡蛋白，细胞色素 C，半胱氨酸蛋白酶-9和半胱氨酸蛋白酶-3 显著增加。17 β-雌二醇诱导则导致完全相反的结果。雌激素受体 (ER) α 的表达被 17 β-雌二醇显著增高，而 ERβ 的表达则在金雀异黄素，白藜芦醇和槲皮素培养基中明显增高。

结论︰