Department of Immunology, School of Medicine, Keimyung University, Dalseo-Gu, Daegu, Republic of Korea.
Oncol Rep. 2013 Jul;30(1):506-12. doi: 10.3892/or.2013.2432. Epub 2013 Apr 26.
RU486 (mifepristone) exerts an anticancer effect on cancer cells via induction of apoptosis. However, the molecular mechanisms are not fully understood. Here, we investigated the effect of RU486 on the apoptosis of U937 human leukemia cells. RU486 markedly increased apoptosis in U937 cells as well as in MDA231 human breast carcinoma, A549 human lung adenocarcinoma epithelial and HCT116 human colorectal carcinoma cells. RU486 increased dose-dependent release of mitochondrial cytochrome c, and reduced the mitochondrial membrane potential (MMP, Δψm) in RU486-treated U937 cells. We also found that overexpression of Bcl-2 completely blocked RU486-mediated apoptosis. However, reactive oxygen species signaling had no effect on RU486-induced apoptosis. RU486 increased the phosphorylation of p38 MAPK and JNK, but p38 MAPK only was associated with RU486-mediated apoptosis. Taken together, RU486 induces apoptosis through reduction in the mitochondrial membrane potential and activation of p38 MAPK in U937 human leukemia cells.
RU486（米非司酮）通过诱导细胞凋亡对癌细胞发挥抗癌作用。然而，其分子机制尚不完全清楚。在这里，我们研究了 RU486 对 U937 人白血病细胞凋亡的影响。RU486 显著增加了 U937 细胞以及 MDA231 人乳腺癌、A549 人肺腺上皮和 HCT116 人结肠直肠癌细胞的凋亡。RU486 增加了线粒体细胞色素 c 的剂量依赖性释放，并降低了 RU486 处理的 U937 细胞中的线粒体膜电位（MMP，Δψm）。我们还发现，Bcl-2 的过表达完全阻断了 RU486 介导的细胞凋亡。然而，活性氧信号对 RU486 诱导的凋亡没有影响。RU486 增加了 p38 MAPK 和 JNK 的磷酸化，但 p38 MAPK 仅与 RU486 介导的细胞凋亡相关。总之，RU486 通过降低 U937 人白血病细胞中线粒体膜电位和激活 p38 MAPK 诱导细胞凋亡。
