Back to Search
Start Over
Resveratrol modulates tumor cell proliferation and protein translation via SIRT1-dependent AMPK activation.
- Source :
-
Journal of agricultural and food chemistry [J Agric Food Chem] 2010 Feb 10; Vol. 58 (3), pp. 1584-92. - Publication Year :
- 2010
-
Abstract
- 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.
- Subjects :
- AMP-Activated Protein Kinases genetics
Animals
Cell Line, Tumor
Enzyme Activation drug effects
Female
Gene Expression drug effects
Humans
Mice
Mice, Inbred BALB C
Mice, Nude
Neoplasms genetics
Neoplasms metabolism
Neoplasms physiopathology
Resveratrol
Signal Transduction drug effects
Sirtuin 1 genetics
Stilbenes administration & dosage
AMP-Activated Protein Kinases metabolism
Cell Proliferation drug effects
Neoplasms drug therapy
Protein Biosynthesis drug effects
Sirtuin 1 metabolism
Stilbenes pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1520-5118
- Volume :
- 58
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Journal of agricultural and food chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 19928762
- Full Text :
- https://doi.org/10.1021/jf9035782