Plant cyclopeptide RA-V kills human breast cancer cells by inducing mitochondria-mediated apoptosis through blocking PDK1-AKT interaction
Plant cyclopeptide RA-V kills human breast cancer cells by inducing mitochondria-mediated apoptosis through blocking PDK1-AKT interaction
复制标题
植物环肽 RA-V 通过阻断 PDK1-AKT 相互作用诱导线粒体介导的细胞凋亡来杀死人类乳腺癌细胞。
DOI：
10.1016/j.taap.2012.12.010
复制
发表时间：
2013-02-15
影响因子：
3.8
通讯作者：
Sun, Yang
中科院分区：
文献类型：
--
作者：
Fang, Xian-Ying;Chen, Wei;Sun, Yang
在本文中，我们研究了天然环肽RA-V对人乳腺癌细胞的作用及其机制。RA-V对人乳腺癌MCF-7、MDA-MB-231细胞和小鼠乳腺癌4 T1细胞的生长有明显的抑制作用。此外，RA-V还可通过线粒体膜电位的降低、细胞色素c的释放和caspase级联反应的激活来触发线粒体凋亡途径。进一步的研究表明，RA-V显着抑制MCF-7细胞中AKT和3-磷酸肌醇依赖性蛋白激酶1（PDK 1）的磷酸化。此外，RA-V破坏了MCF-7细胞中PDK 1和AKT之间的相互作用。此外，在所有三种乳腺癌细胞中，磷脂酰肌醇3-激酶抑制剂均可增强RA-V诱导的细胞凋亡，而AKT过表达则可减弱RA-V诱导的细胞凋亡。综上所述，本研究表明，RA-V，可以诱导细胞凋亡介导的，对人类乳腺癌发挥强大的抗肿瘤活性。RA-V的潜在抗癌机制与阻断PDK 1和AKT之间的相互作用有关。(C)2012 Elsevier Inc. All rights reserved.
In the present paper, we examined the effects of a natural cyclopeptide RA-V on human breast cancer cells and the underlying mechanisms. RA-V significantly inhibited the growth of human breast cancer MCF-7, MDA-MB-231 cells and murine breast cancer 4T1 cells. In addition, RA-V triggered mitochondria] apoptotic pathway which was indicated by the loss of mitochondrial membrane potential, the release of cytochrome c, and the activation of caspase cascade. Further study showed that RA-V dramatically inhibited phosphorylation of AKT and 3-phosphoinositide dependent protein kinase 1 (PDK1) in MCF-7 cells. Moreover, RA-V disrupted the interaction between PDK1 and AKT in MCF-7 cells. Furthermore, RA-V-induced apoptosis could be enhanced by phosphatidylinositol 3-kinase inhibitor or attenuated by over-expression of AKT in all the three kinds of breast cancer cells. Taken together, this study shows that RA-V, which can induce mitochondria-mediated apoptosis, exerts strong anti-tumor activity against human breast cancer. The underlying anti-cancer mechanism of RA-V is related to the blockage of the interaction between PDK1 and AKT. (C) 2012 Elsevier Inc. All rights reserved.