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

Abstract：

: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.

journal_name

Acta Pharmacol Sin

journal_title

Acta pharmacologica Sinica

authors

Guan YD,Jiang SL,Yu P,Wen M,Zhang Y,Xiao SS,Xu XJ,Cheng Y

doi

10.1038/aps.2017.139

subject

Has Abstract

pub_date

2018-04-01 00:00:00

pages

642-648

issue

4

eissn

1671-4083

issn

1745-7254

pii

aps2017139

journal_volume

39

pub_type

杂志文章

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