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.
Anticancer Res. 2011 Oct;31(10):3301-13.
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.
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.
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.
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.
植物雌激素已知可预防肿瘤诱导。但其作用的分子机制在很大程度上尚不清楚。本研究旨在研究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。
通过增殖测定法测试植物雌激素的抗增殖作用。通过流式细胞术分析细胞周期。通过 Western blot 测定植物雌激素对细胞信号分子的影响。
染料木黄酮和槲皮素抑制 MCF-7 vec 和 MCF-7 HER2 细胞的增殖。这种生长抑制伴随着 subG0/G1 凋亡分数的增加。染料木黄酮和槲皮素诱导了细胞外凋亡途径，上调了 p53。染料木黄酮和槲皮素降低了 IκBα 的磷酸化水平，并阻止了 p65 的核转位及其在核内的磷酸化。
染料木黄酮和槲皮素通过抑制 NFκB 信号通路发挥其抗增殖活性。植物雌激素可能是预防或治疗 HER2 过表达乳腺癌的潜在有用化合物。
