Resveratrol is reported to possess chemotherapeutic properties in several cancers. In this study, we wanted to investigate
the molecular mechanisms of resveratrol-induced cell cycle arrest and apoptosis as well as the impact of resveratrol on
NAMPT and SIRT1 protein function and asked whether there are differences in hepatocarcinoma cells (HepG2, Hep3B cells)
and non-cancerous primary human hepatocytes. We found a lower basal NAMPT mRNA and protein expression in
hepatocarcinoma cells compared to primary hepatocytes. In contrast, SIRT1 was significantly higher expressed in
hepatocarcinoma cells than in primary hepatocytes. Resveratrol induced cell cycle arrest in the S- and G2/M- phase and
apoptosis was mediated by activation of p53 and caspase-3 in HepG2 cells. In contrast to primary hepatocytes, resveratrol
treated HepG2 cells showed a reduction of NAMPT enzymatic activity and increased p53 acetylation (K382). Resveratrol
induced NAMPT release from HepG2 cells which was associated with increased NAMPT mRNA expression. This effect was
absent in primary hepatocytes where resveratrol was shown to function as NAMPT and SIRT1 activator. SIRT1 inhibition by
EX527 resembled resveratrol effects on HepG2 cells. Furthermore, a SIRT1 overexpression significantly decreased both p53
hyperacetylation and resveratrol-induced NAMPT release as well as S-phase arrest in HepG2 cells. We could show that
NAMPT and SIRT1 are differentially regulated by resveratrol in hepatocarcinoma cells and primary hepatocytes and that
resveratrol did not act as a SIRT1 activator in hepatocarcinoma cells.
| Identifer | oai:union.ndltd.org:DRESDEN/oai:qucosa:de:qucosa:12437 |
| Date | January 2014 |
| Creators | Schuster, Susanne, Garten, Antje |
| Contributors | Universität Leipzig, Public Library of Science |
| Source Sets | Hochschulschriftenserver (HSSS) der SLUB Dresden |
| Language | English |
| Detected Language | English |
| Type | doc-type:article, info:eu-repo/semantics/article, doc-type:Text |
| Source | PLoS ONE, March 06, 2014 doi: 10.1371/journal.pone.0091045 |
| Rights | info:eu-repo/semantics/openAccess |
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