PT  - JOURNAL ARTICLE
AU  - Ursula G. B. Haider
AU  - Dan Sorescu
AU  - Kathy K. Griendling
AU  - Angelika M. Vollmar
AU  - Verena M. Dirsch
TI  - Resveratrol Increases Serine<sup>15</sup>-Phosphorylated but Transcriptionally Impaired p53 and Induces a Reversible  DNA Replication Block in Serum-Activated Vascular Smooth Muscle Cells
AID  - 10.1124/mol.63.4.925
DP  - 2003 Apr 01
TA  - Molecular Pharmacology
PG  - 925--932
VI  - 63
IP  - 4
4099  - http://molpharm.aspetjournals.org/content/63/4/925.short
4100  - http://molpharm.aspetjournals.org/content/63/4/925.full
SO  - Mol Pharmacol2003 Apr 01; 63
AB  - Resveratrol (RV), a polyphenolic stilbene derivative, has been proposed to exert a plethora of beneficial cardiovascular effects. Of these, in particular, inhibition of vascular smooth muscle cell (VSMC) proliferation shows great promise for preventing cardiovascular disease. In the present study, we show that RV leads to a reversible arrest in early S phase of the VSMC cycle, accompanied by an accumulation of hyperphosphorylated retinoblastoma protein. In contrast to studies with other cell systems, RV decreases cellular levels of the cyclin-dependent kinase inhibitors p21Cip1 and p27Kip1. This is of particular interest because phosphorylated p53 protein (serine15) is strongly enhanced by this substance. We further found that RV only slightly inhibits phosphorylation of Erk 1/2, protein kinase B/Akt, and p70S6 kinase upon serum stimulation. Thus, inhibition of these kinases is not likely to contribute to the cell cycle effect of RV. Importantly, the observed S phase arrest is not linked to an increase in apoptotic cell death: there was no detectable increase in apoptotic nuclei and in levels of the proapoptotic protein Bax. This is the first study elucidating the molecular pathways mediating the antiproliferative properties of RV in VSMCs. The American Society for Pharmacology and Experimental Therapeutics