Anticancer Research, 2011, 31(10):3301-13.

Phytoestrogens Induce Apoptosis via Extrinsic Pathway, Inhibiting Nuclear Factor-κB Signaling in HER2-overexpressing Breast Cancer Cells

Hye Sook Seo, et al

Laboratory of Clinical Biology and Pharmacogenomics and Center for Clinical Research and Genomics, Institute of Oriental Medicine, Kyung Hee University, 1 Hoegi-dong, Dongdaemun-gu, Seoul 130-701, Republic of Korea; et al

BACKGROUND: Phytoestrogens are known to prevent tumor induction. But their molecular mechanisms of action are largely unknown. This study aimed to examine the effect of genistein and quercetin on proliferation and apoptosis in HER2-expressing breast cancer cells.

MATERIALS AND METHODS: The antiproliferative effects of phytoestrogens were tested by proliferation assays. Flow cytometry was performed to analyze the cell cycle. The effect of phytoestrogens on cell-signaling molecules was determined by Western blotting.

RESULTS: Genistein and quercetin inhibited the proliferation of MCF-7 vec and MCF-7 HER2 cells. This growth inhibition was accompanied with an increase of subG(0)/G(1) apoptotic fractions. Genistein and quercetin induced extrinsic apoptosis pathway, up-regulating p53. Genistein and quercetin reduced the phosphorylation level of IκBα, and abrogated the nuclear translocation of p65 and its phosphorylation within the nucleus.

CONCLUSION: Genistein and quercetin exert their antiproliferative activity by inhibiting NFκB signaling. Phytoestrogens could be potential useful compounds to prevent or treat HER2-overexpressing breast cancer.

希腊《抗癌研究》，2011年10月

在 HER2-过表达的乳腺癌细胞中植物雌激素通过外在通路诱导细胞凋亡，抑制细胞核因子-κB 信号

金惠淑等

韩国首尔庆熙大学东方医学研究所临床生物学和药物基因组学实验室与临床研究和基因组学研究中心

背景︰ 已知植物雌激素可以防止肿瘤诱发。但是其作用的分子机制在很大程度上未知。本研究旨在探讨染料木黄酮和槲皮素对 HER2 表达的乳腺癌细胞增殖和凋亡的影响。

材料和方法︰用增生试验测试植物雌激素的抗增殖作用。用流式细胞仪分析细胞周期。用免疫印迹法测定植物雌激素对细胞信号转导分子的影响。

结果︰ 染料木黄酮和槲皮素抑制 MCF-7 血管内皮细胞和MCF-7 HER2的细胞增殖。这种增长抑制伴随着subG(0)/G(1) 凋亡分数的增加。染料木黄酮和槲皮素诱导外源性细胞凋亡通路，上调 p53。染料木黄酮和槲皮素降低了IκBα的磷酸化水平并取消了细胞核p65的易位和细胞核内的磷酸化。

结论︰ 染料木黄酮和槲皮素通过抑制NFκB信号发挥其抗增殖活性。植物雌激素可能是潜在有用的化合物来预防或治疗 HER2 过表达的乳腺癌。