PMID- 25088800
OWN - NLM
STAT- MEDLINE
DCOM- 20141217
LR  - 20220318
IS  - 1349-7006 (Electronic)
IS  - 1347-9032 (Print)
IS  - 1347-9032 (Linking)
VI  - 105
IP  - 10
DP  - 2014 Oct
TI  - Ampelopsin-induced autophagy protects breast cancer cells from apoptosis through 
      Akt-mTOR pathway via endoplasmic reticulum stress.
PG  - 1279-87
LID - 10.1111/cas.12494 [doi]
AB  - Our previous study has shown that ampelopsin (AMP), a flavonol mainly found in 
      Ampelopsis 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 (LC3B-II) and the 
      conversion of LC3B-I to LC3B-II, the degradation of the selective autophagic 
      target p62/SQSTM1, and the formation of green fluorescent protein (GFP)-LC3 
      puncta. Blockage of autophagy augmented AMP-induced cell death, suggesting that 
      autophagy has cytoprotective effects. Meanwhile, AMP treatment suppressed 
      Akt-mammalian target of rapamycin (mTOR) pathway as evidenced by dose- and 
      time-dependent decrease of the phosphorylation of Akt, mTOR and ribosomal protein 
      S6 kinase (p70S6K), whereas Akt activator insulin-like growth factor-1 (IGF-1) 
      pretreatment partially restored Akt-mTOR pathway inhibited by AMP and decreased 
      AMP-inuduced autophagy, signifying that AMP activated autophagy via inhibition of 
      the Akt-mTOR pathway. Additionally, blocking ER stress not only reduced autophagy 
      induction, but also alleviated inhibition of the Akt-mTOR pathway induced by AMP, 
      suggesting that activation of ER stress was involved in induction of autophagy 
      and inhibition of the Akt-mTOR pathway. Taken together, these findings indicate 
      that AMP induces protective autophagy in human breast cancer cells through 
      Akt-mTOR pathway via ER stress.
CI  - (c) 2014 The Authors. Cancer Science published by Wiley Publishing Asia Pty Ltd on 
      behalf of Japanese Cancer Association.
FAU - Zhou, Yong
AU  - Zhou Y
AD  - Research Center for Nutrition and Food Safety, Institute of Military Preventive 
      Medicine, Third Military Medical University, Chongqing Key Laboratory of 
      Nutrition and Food Safety, Research Center for Medical Nutrition, Chongqing, 
      China.
FAU - Liang, Xinyu
AU  - Liang X
FAU - Chang, Hui
AU  - Chang H
FAU - Shu, Furong
AU  - Shu F
FAU - Wu, Ying
AU  - Wu Y
FAU - Zhang, Ting
AU  - Zhang T
FAU - Fu, Yujie
AU  - Fu Y
FAU - Zhang, Qianyong
AU  - Zhang Q
FAU - Zhu, Jun-Dong
AU  - Zhu JD
FAU - Mi, Mantian
AU  - Mi M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140918
PL  - England
TA  - Cancer Sci
JT  - Cancer science
JID - 101168776
RN  - 0 (Flavonoids)
RN  - 27200-12-0 (ampelopsin)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Apoptosis/*drug effects
MH  - Autophagy/*drug effects
MH  - Breast Neoplasms/*drug therapy/pathology
MH  - Cell Line, Tumor
MH  - Endoplasmic Reticulum Stress/*physiology
MH  - Female
MH  - Flavonoids/*pharmacology
MH  - Humans
MH  - Proto-Oncogene Proteins c-akt/antagonists & inhibitors/*physiology
MH  - Signal Transduction/drug effects/physiology
MH  - TOR Serine-Threonine Kinases/antagonists & inhibitors/*physiology
PMC - PMC4462353
OTO - NOTNLM
OT  - Ampelopsin
OT  - autophagy
OT  - breast cancer
OT  - endoplasmic reticulum stress
OT  - mammalian target of rapamycin
EDAT- 2014/08/05 06:00
MHDA- 2014/12/18 06:00
PMCR- 2014/10/01
CRDT- 2014/08/05 06:00
PHST- 2014/04/08 00:00 [received]
PHST- 2014/07/01 00:00 [revised]
PHST- 2014/07/23 00:00 [accepted]
PHST- 2014/08/05 06:00 [entrez]
PHST- 2014/08/05 06:00 [pubmed]
PHST- 2014/12/18 06:00 [medline]
PHST- 2014/10/01 00:00 [pmc-release]
AID - 10.1111/cas.12494 [doi]
PST - ppublish
SO  - Cancer Sci. 2014 Oct;105(10):1279-87. doi: 10.1111/cas.12494. Epub 2014 Sep 18.