Department of Pharmacology, Changhua Christian Hospital, 135 Nanhsiao St., Changhua, Taiwan.
Hum Exp Toxicol. 2009 Aug;28(8):493-503. doi: 10.1177/0960327109107002. Epub 2009 Sep 15.
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 Ca(2+) levels and reduced the mitochondrial membrane potential (DeltaPsi(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.
最近有相当多的证据表明，类黄酮具有抗肿瘤作用。槲皮素是一种普遍存在的生物活性类黄酮，可抑制不同类型的癌细胞增殖，诱导细胞周期停滞和细胞凋亡。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细胞活力的影响，并确定其在人乳腺癌 MDA-MB-231 细胞中的作用机制。槲皮素呈剂量和时间依赖性地降低活细胞的百分比，这与细胞周期停滞和细胞凋亡有关。槲皮素不会增加活性氧的产生，但会增加细胞浆 Ca(2+)水平并降低线粒体膜电位（ΔPsi(m)）。槲皮素处理促进 MDA-MB-231 细胞中 caspase-3、-8 和 -9 的激活。半胱氨酸蛋白酶抑制剂可阻止槲皮素诱导的细胞活力丧失。槲皮素增加促凋亡蛋白 Bax 的丰度，降低抗凋亡蛋白 Bcl-2 的水平。共聚焦激光显微镜检查表明，槲皮素促进凋亡诱导因子（AIF）从线粒体释放，并刺激向核内易位。综上所述，这些发现表明，槲皮素通过线粒体和 caspase-3 依赖性途径导致人乳腺癌 MDA-MB-231 细胞死亡。
