Antiproliferative Activity of Resveratrol, a Potential Inhibitor of Ribonucleotide Reductase.
Presented by: Douglas Davidson
Mentor: C.K. Mathews
Dept. of Biochemistry & Biophysics, Oregon State University
: Resveratrol, a naturally found phytoalexin in grapes and peanuts, is well known for its presumed role in the prevention of heart disease, an effect associated with red wine consumption. Resveratrol has been reported to quench the catalytically essential tyrosyl radical in the small subunit (R2) of ribonucleotide reductase, the enzyme responsible for supplying the dNTPs in DNA replication. Since deoxyribonucleoside triphosphates are required for DNA synthesis, ribonucleotide reductase is a natural target for anticancer and antiproliferative drugs. Because of this, resveratrol has led many to consider this naturally occurring antioxidant to be an anticancer and antiviral agent, yet with little reported toxicity.
The project objective is to assay both mammalian and viral ribonucleotide reductase (RNR) activity in a novel assay that simultaneously monitors reduction of all four of its ribonucleoside diphosphate substrates. This assay will be carried out using purified recombinant mouse and vaccinia virus RNR, and should clearly show whether resveratrol inhibits RNR. If so, this investigafion will be extended to look at the possible differenfial effects of resveratrol upon the deoxyribonucleoside triphosphates pools of intact mammalian cells.