PMID- 19928762
OWN - NLM
STAT- MEDLINE
DCOM- 20100419
LR  - 20181201
IS  - 1520-5118 (Electronic)
IS  - 0021-8561 (Linking)
VI  - 58
IP  - 3
DP  - 2010 Feb 10
TI  - Resveratrol modulates tumor cell proliferation and protein translation via 
      SIRT1-dependent AMPK activation.
PG  - 1584-92
LID - 10.1021/jf9035782 [doi]
AB  - Resveratrol functions as an agonist for estrogen receptor (ER)-mediated 
      transcription. However, other researchers have reported that resveratrol 
      decreases proliferation of breast cancer cells that are either ER-positive or 
      ER-negative, which suggests that the interaction of resveratrol with the ER may 
      not fully explain its inhibitory effect on proliferation. Similar to those 
      effects associated with caloric restriction (CR), resveratrol has multiple 
      beneficial activities, such as increased life span and delay in the onset of 
      diseases associated with aging. One key enzyme thought to be activated during CR 
      is the AMP-activated kinase (AMPK), a sensor of cellular energy levels. The 
      suppression of nonessential energy expenditure by activated AMPK along with the 
      CR mimetic and antiproliferative properties of resveratrol has led us to 
      hypothesize that resveratrol activity might have an important role in the 
      activation of AMPK. Here, we show that resveratrol activated AMPK in both 
      ER-positive and ER-negative breast cancer cells. Once activated, AMPK inhibited 
      4E-BP1 signaling and mRNA translation via mammalian target of rapamycin (mTOR). 
      Moreover, we also found that AMPK activity mediated by resveratrol in cancer 
      cells was due to inducing the expression of Sirtuin type 1 (SIRT1) via elevation 
      in the cellular NAD(+)/NADH in ER-positive cells. To our knowledge, we 
      demonstrate here for the first time that resveratrol induces the expression of 
      SIRT1 protein in human cancer cells. These observations raise the possibility 
      that SIRT1 functions as a novel upstream regulator for AMPK signaling and may 
      additionally modulate tumor cell proliferation. Targeting SIRT1/AMPK signaling by 
      resveratrol may have potential therapeutic implications for cancer and 
      age-related diseases.
FAU - Lin, Jia-Ni
AU  - Lin JN
AD  - The PhD Program for Cancer Biology and Drug Discovery, College of Pharmacy, China 
      Medical University, Taichung, Taiwan.
FAU - Lin, Victor Chia-Hsiang
AU  - Lin VC
FAU - Rau, Kun-Ming
AU  - Rau KM
FAU - Shieh, Po-Chuen
AU  - Shieh PC
FAU - Kuo, Daih-Huang
AU  - Kuo DH
FAU - Shieh, Jia-Ching
AU  - Shieh JC
FAU - Chen, Wei-Jen
AU  - Chen WJ
FAU - Tsai, Shih-Chang
AU  - Tsai SC
FAU - Way, Tzong-Der
AU  - Way TD
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Agric Food Chem
JT  - Journal of agricultural and food chemistry
JID - 0374755
RN  - 0 (Stilbenes)
RN  - EC 2.7.11.31 (AMP-Activated Protein Kinases)
RN  - EC 3.5.1.- (SIRT1 protein, human)
RN  - EC 3.5.1.- (Sirtuin 1)
RN  - Q369O8926L (Resveratrol)
SB  - IM
MH  - AMP-Activated Protein Kinases/genetics/*metabolism
MH  - Animals
MH  - Cell Line, Tumor
MH  - Cell Proliferation/*drug effects
MH  - Enzyme Activation/drug effects
MH  - Female
MH  - Gene Expression/drug effects
MH  - Humans
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Mice, Nude
MH  - Neoplasms/*drug therapy/genetics/metabolism/physiopathology
MH  - Protein Biosynthesis/*drug effects
MH  - Resveratrol
MH  - Signal Transduction/drug effects
MH  - Sirtuin 1/genetics/*metabolism
MH  - Stilbenes/administration & dosage/*pharmacology
EDAT- 2009/11/26 06:00
MHDA- 2010/04/20 06:00
CRDT- 2009/11/26 06:00
PHST- 2009/11/26 06:00 [entrez]
PHST- 2009/11/26 06:00 [pubmed]
PHST- 2010/04/20 06:00 [medline]
AID - 10.1021/jf9035782 [doi]
PST - ppublish
SO  - J Agric Food Chem. 2010 Feb 10;58(3):1584-92. doi: 10.1021/jf9035782.