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

Yi-di GUAN1, Shi-long JIANG1, Pian YU1, Mei WEN1, Yi ZHANG2, Song-shu XIAO3, Xiao-jun XU4,5, Yan CHENG1
1 Xiangya School of Pharmaceutical Sciences, Central South University, Changsha 410008, China
2 Department of Pharmacology, College of Pharmaceutical Sciences, Soochow University, Suzhou 215123, China
3 Department of Gynecology and Obstetrics, the Third Xiangya Hospital, Central South University, Changsha 410008, China
4 State Key Laboratory of Natural
5 Medicines, China Pharmaceutical University, Nanjing 210009, China
Correspondence to: Song-shu XIAO:, Xiao-jun XU:, Yan CHENG:,
DOI: 10.1038/aps.2017.139
Received: 14 December 2017
Accepted: 5 June 2017
Advance online: 16 August 2017


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.
Keywords: human breast cancer; raddeanin A; traditional Chinese medicine; autophagy; apoptosis; eEF-2K; chloroquine

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