Theaflavins retard human breast cancer cell migration by inhibiting NF-κB via p53-ROS cross-talk
Theaflavins retard human breast cancer cell migration by inhibiting NF-κB via p53-ROS cross-talk
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DOI：
10.1016/j.febslet.2009.10.081
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发表时间：
2010-01-04
期刊：
影响因子：
3.5
通讯作者：
Das, Tanya
中科院分区：
文献类型：
--
作者：
Adhikary, Arghya;Mohanty, Suchismita;Das, Tanya
目前的研究表明，茶黄素利用p53阻止人类乳腺癌细胞的转移。我们的数据表明，p53依赖性活性氧（ROS）通过p38 MAPK在反馈回路中诱导p53磷酸化，从而抑制I κ B α磷酸化和NF-κ B/p65核转位，从而下调转移蛋白金属蛋白酶（MMP）-2和MMP-9。当表达野生型p53的MCF-7细胞用p53短干扰RNA转染，或用ROS的药理学抑制剂处理时，茶黄素不能抑制NF-κ B介导的细胞迁移。另一方面，NF-κ B过表达赋予MCF-7细胞对茶黄素的抗迁移作用的抗性。这些结果表明，通过p53-ROS串扰抑制NF-κ B是茶黄素在乳腺癌细胞中实现抗迁移作用的先决条件。
The present study demonstrates that theaflavins exploit p53 to impede metastasis in human breast cancer cells. Our data suggest that p53-dependent reactive oxygen species (ROS) induce p53-phosphorylation via p38MAPK in a feedback loop to inhibit I kappa B alpha-phosphorylation and NF-kappa B/p65 nuclear translocation, thereby down-regulating the metastatic proteins metalloproteinase (MMP)-2 and MMP-9. When wild-type p53-expressing MCF-7 cells are transfected with p53 short-interfering RNA, or treated with a pharmacological inhibitor of ROS, theaflavins fail to inhibit NF-kappa B-mediated cell migration. On the other hand, NF-kappa B over-expression bestows MCF-7 cells with resistance to the anti-migratory effect of theaflavins. These results indicate that inhibition of NF-kappa B via p53-ROS crosstalk is a pre-requisite for theaflavins to accomplish the anti-migratory effect in breast cancer cells.