Suppression of eEF-2K-mediated autophagy enhances the cytotoxicity of raddeanin A against human breast cancer cells in vitro

• 来源期刊: 中国药理学报（英文版）
• 关键词: human breast cancer raddeanin A traditional Chinese medicine autophagy apoptosis eEF-2K chloroquine
• 年，卷（期）: 2018,（4）
• 页码范围: 642-648
• 页数: 7页
• 语种: 英文
• DOI: 10.1038/aps.2017.139

摘要

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 (2-8μmol/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.