Deguelin Inhibits Growth of Breast Cancer Cells by Modulating the Expression of Key Members of the Wnt Signaling Pathway
Deguelin Inhibits Growth of Breast Cancer Cells by Modulating the Expression of Key Members of the Wnt Signaling Pathway
复制标题
DOI：
10.1158/1940-6207.capr-08-0232
复制
发表时间：
2009-11-01
影响因子：
3.3
通讯作者：
Mehta, Rajendra G.
中科院分区：
文献类型：
--
作者：
Murillo, Genoveva;Peng, Xinjian;Mehta, Rajendra G.
强调早期发现和更有效的治疗已经降低了乳腺癌的死亡率。尽管有所下降，但乳腺癌仍然是40至55岁妇女的主要死因，是妇女死亡的第二大总原因。因此，本研究的目的是评估鱼藤素的治疗效果，鱼藤素是一种从几种植物中分离的类鱼藤素，据报道其在皮肤癌、乳腺癌、结肠癌和肺癌中具有化学预防和/或化学治疗作用。以MCF-7、BT474、T47 D和MDA-MB-231四种人乳腺癌细胞株为实验材料，通过细胞计数和MTT法检测鱼藤素对细胞增殖的影响。吖啶/乙啶染色和DNA梯状电泳检测细胞凋亡。通过微阵列分析评估鱼藤素处理后MDA-MB-231细胞中的基因表达变化。发现1 μ mol/L鱼藤素抑制所测试的乳腺癌细胞系的生长，范围为37%至87%。对于MDA-MB-231细胞系注意到最高抑制（MDA-MB-231>BT474> MCF 7> T47 D> MCF 12 F）。鱼藤素处理后的MDA-MB-231细胞出现S期阻滞和凋亡。微阵列图谱表明两个独立途径的差异表达，包括鱼藤素处理导致细胞中的细胞凋亡和Wnt/β-连环蛋白信号传导基因簇。这些研究支持鱼藤素在人乳腺癌细胞中的抗增殖作用，也许更重要的是，说明了鱼藤素在Wnt信号通路中的新作用。
An emphasis in earlydetection and more effective treatments has decreased the mortality rate of breast cancer. Despite this decrease, breast cancer continues to be the leading cause of death among women between 40 and 55 years of age and is the second overall cause of death among women. Hence, the aim of the present study was to assess the therapeutic efficacy of deguelin, a rotenoid isolated from several plant species, which has been reported to have chemopreventive and/or chemotherapeutic effects in skin, mammary, colon, and lung cancers. The effect of deguelin on cell proliferation was evaluated using four human breast carcinoma cell lines (MCF-7, BT474, T47D, and MDA-MB-231) by cell count and MTT. Moreover, apoptosis was evaluated by acridine/ethidium staining and DNA laddering. Gene expression changes following deguelin treatment in MDA-MB-231 cells was assessed through microarray analysis. Deguelin at 1 mu mol/L was found to inhibit the growth of the breast cancer cell lines tested with a range of 37% to 87%. The highest inhibition was noted for the MDA-MB-231 cell line (MDA-MB-231>BT474>MCF7>T47D>MCF12F). An arrest at the S phase of the cell cycle and apoptosis were shown in the MDA-MB-231 cells treated with deguelin. The microarray profile indicated differential expression of two independent pathways, including clusters of apoptosis and Wnt/beta-catenin signaling genes in cells as a result of deguelin treatment. These studies support the antiproliferative effects of deguelin in human breast cancer cells and, perhaps more importantly, illustrate novel actions by deguelin in the Wnt signaling pathway.