Suppression of eEF-2K-mediated autophagy enhances the cytotoxicity of raddeanin A against human breast cancer cells in vitro
Suppression of eEF-2K-mediated autophagy enhances the cytotoxicity of raddeanin A against human breast cancer cells in vitro
复制标题
抑制 eEF-2K 介导的自噬增强了 raddeanin A 对人乳腺癌细胞的体外细胞毒性
DOI：
10.1038/aps.2017.139
复制
发表时间：
2018-04-01
影响因子：
8.2
通讯作者：
Cheng, Yan
中科院分区：
文献类型：
--
作者：
Guan, Yi-di;Jiang, Shi-long;Cheng, Yan
海葵苷A （raddeanin A， RA）是一种从海葵中提取的齐墩烷型三萜皂苷，具有显著的体外和体内抗癌作用。此外，还发现RA能激活人胃癌细胞的自噬。在本研究中，我们在体外研究了ra诱导乳腺癌细胞自噬的分子机制，以及ra诱导的自噬与其细胞毒性的关系。在乳腺癌细胞系T47D、MCF-7和MDA-MB-231中LC3水平的升高证明，RA （2-8 μmol/L）剂量依赖性地增强了自噬。此外，Akt-mTOR-eEF-2K信号通路被证明参与了ra诱导的3种乳腺癌细胞系的自噬激活。RA （2 ~ 10 μmol/L）剂量依赖性诱导3株乳腺癌细胞凋亡。自噬抑制剂氯喹（CQ, 20 μmol/L）预处理通过促进细胞凋亡显著增强ra引起的细胞毒性。综上所述，我们的研究结果表明，调节自噬可以增强RA对人乳腺癌细胞的细胞毒性。
Recent evidence shows that raddeanin A (RA), an oleanane-type triterpenoid saponin extracted from Anemone raddeana Regel, exerts remarkable cytotoxicity against cancer cells in vitro and in vivo. In addition, RA has also been found to activate autophagy in human gastric cancer cells. In this study, we investigated the molecular mechanisms underlying RA-induced autophagy as well as the relationship between RA-induced autophagy and its cytotoxicity in human breast cancer cells in vitro. Treatment with RA (2–8 μmol/L) dose-dependently enhanced autophagy, as evidenced by increased LC3 levels in breast cancer cell lines T47D, MCF-7 and MDA-MB-231. Furthermore, the Akt-mTOR-eEF-2K signaling pathway was demonstrated to be involved in RA-induced activation of autophagy in the 3 breast cancer cell lines. Treatment with RA (2–10 μmol/L) dose-dependently induced apoptosis in the 3 breast cancer cell lines. Pretreatment with the autophagy inhibitor chloroquine (CQ, 20 μmol/L) significantly enhanced RA-caused cytotoxicity via promoting apoptosis. In conclusion, our results suggest that modulating autophagy can reinforce the cytotoxicity of RA against human breast cancer cells.