Quercetin-induced apoptosis acts through mitochondrial- and caspase-3-dependent pathways in human breast cancer MDA-MB-231 cells
Quercetin-induced apoptosis acts through mitochondrial- and caspase-3-dependent pathways in human breast cancer MDA-MB-231 cells
复制标题
DOI：
10.1177/0960327109107002
复制
发表时间：
2009-08-01
影响因子：
2.8
通讯作者：
Chen, Dar-Ren
中科院分区：
文献类型：
--
作者：
Chien, Su-Yu;Wu, Yao-Chung;Chen, Dar-Ren
最近有大量证据表明黄酮醇具有抗肿瘤作用。槲皮素是一种普遍存在的具有生物活性的黄酮醇，在不同的肿瘤细胞类型中抑制细胞增殖，诱导细胞周期阻滞和凋亡。槲皮素诱导人乳腺癌细胞凋亡的确切分子机制尚不清楚。本研究旨在探讨槲皮素对人乳腺癌MDA-MB-231细胞活力的影响及其机制。槲皮素以剂量和时间依赖性方式降低活细胞的百分比，这与细胞周期阻滞和凋亡有关。槲皮素不增加活性氧的产生，但增加胞质Ca 2+水平，降低线粒体膜电位（Δ Psi（m））。槲皮素处理促进MDA-MB-231细胞中caspase-3、-8和-9的活化。半胱天冬酶抑制剂防止了槲皮素诱导的细胞活力丧失。槲皮素增加了促凋亡蛋白Bax的丰度，降低了抗凋亡蛋白Bcl-2的水平。激光共聚焦显微镜检查表明，槲皮素促进凋亡诱导因子（AIF）从线粒体释放，并刺激易位到细胞核。综上所述，这些发现表明槲皮素导致人乳腺癌MDA-MB-231细胞死亡，通过细胞凋亡和caspase-3依赖性途径。
There has been considerable evidence recently demonstrating the anti-tumour effects of flavonols. Quercetin, an ubiquitous bioactive flavonol, inhibits cells proliferation, induces cell cycle arrest and apoptosis in different cancer cell types. The precise molecular mechanism of quercetin-induced apoptosis in human breast cancer cells is unclear. The purpose of this study was to investigate effects of quercetin on cell viability and to determine its underlying mechanism in human breast cancer MDA-MB-231 cells. Quercetin decreased the percentage of viable cells in a dose- and time-dependent manner, which was associated with cell cycle arrest and apoptosis. Quercetin did not increase reactive oxygen species generation but increased cytosolic Ca2+ levels and reduced the mitochondrial membrane potential (Delta Psi(m)). Quercetin treatment promoted activation of caspase-3, -8 and -9 in MDA-MB-231 cells. Caspase inhibitors prevented the quercetin-induced loss of cell viability. Quercetin increased abundance of the pro-apoptotic protein Bax and decreased the levels of anti-apoptotic protein Bcl-2. Confocal laser microscope examination indicated that quercetin promoted apoptosis-inducing factor (AIF) release from mitochondria and stimulated translocation to the nucleus. Taken together, these findings suggest that quercetin results in human breast cancer MDA-MB-231 cell death through mitochondrial-and caspase-3-dependent pathways.