Open AccessAmpelopsin‐induced autophagy protects breast cancer cells from apoptosis through A kt‐m TOR pathway via endoplasmic reticulum stress
Author(s) -
Zhou Yong,
Liang Xinyu,
Chang Hui,
Shu Furong,
Wu Ying,
Zhang Ting,
Fu Yujie,
Zhang Qianyong,
Zhu JunDong,
Mi Mantian
Publication year - 2014
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.12494
Subject(s) - autophagy , pi3k/akt/mtor pathway , protein kinase b , endoplasmic reticulum , unfolded protein response , microbiology and biotechnology , programmed cell death , chemistry , phosphorylation , signal transduction , apoptosis , biology , biochemistry
Our previous study has shown that ampelopsin ( AMP ), a flavonol mainly found in A mpelopsis grossedentata , could induce cell death in human breast cancer cells via reactive oxygen species generation and endoplasmic reticulum ( ER ) stress pathway. Here, we examined whether autophagy is activated in AMP ‐treated breast cancer cells and, if so, sought to find the exact role and underlying molecular profile of autophagy in AMP ‐induced cell death. Our results showed that AMP treatment activated autophagy in MDA ‐ MB ‐231 and MCF ‐7 breast cancer cells, as evidenced by the accumulation of autophagosomes, an increase of microtubule‐associated protein 1 light chain 3 beta‐2 ( LC 3 B ‐ II ) and the conversion of LC 3 B ‐ I to LC 3 B ‐ II , the degradation of the selective autophagic target p62/ SQSTM 1, and the formation of green fluorescent protein ( GFP )‐ LC 3 puncta. Blockage of autophagy augmented AMP ‐induced cell death, suggesting that autophagy has cytoprotective effects. Meanwhile, AMP treatment suppressed A kt‐mammalian target of rapamycin (m TOR ) pathway as evidenced by dose‐ and time‐dependent decrease of the phosphorylation of A kt, m TOR and ribosomal protein S 6 kinase (p70 S 6 K ), whereas A kt activator insulin‐like growth factor‐1 ( IGF ‐1) pretreatment partially restored A kt‐m TOR pathway inhibited by AMP and decreased AMP ‐inuduced autophagy, signifying that AMP activated autophagy via inhibition of the A kt‐m TOR pathway. Additionally, blocking ER stress not only reduced autophagy induction, but also alleviated inhibition of the A kt‐m TOR pathway induced by AMP , suggesting that activation of ER stress was involved in induction of autophagy and inhibition of the A kt‐m TOR pathway. Taken together, these findings indicate that AMP induces protective autophagy in human breast cancer cells through A kt‐m TOR pathway via ER stress.