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Vß3 contains a receptor site for resveratrol
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* Stratton Veterans Affairs Medical Center and
Ordway Research Institute, Albany, New York, USA;
Laboratoire de Mycologie et Biotechnologie Vegetale, Université de Bordeaux, Bordeaux, Cedex, France; and
Albany Medical College and
|| Wadsworth Center, New York State Department of Health, Albany, New York, USA
1Correspondence: Ordway Research Institute, 150 New Scotland Ave., Albany, NY 12208, USA. E-mail: fdavis{at}ordwayresearch.org
ABSTRACT
Resveratrol is a naturally occurring polyphenol, which causes apoptosis in cultured cancer cells. We describe a cell surface resveratrol receptor on the extracellular domain of hetero-dimeric 
Vß3 integrin in MCF-7 human breast cancer cells. This receptor is linked to induction by resveratrol of extracellular-regulated kinases 1 and 2 (ERK1/2)- and serine-15-p53-dependent phosphorylation leading to apoptosis. The integrin receptor is near the Arg-Gly-Asp (RGD) recognition site on the integrin; an integrin-binding RGD peptide inhibits induction by resveratrol of ERK1/2- and p53-dependent apoptosis. Antibody (Ab) to integrin Vß3, but not to Vß5, inhibits activation by resveratrol of ERK1/2 and p53 and consequent apoptosis in estrogen receptor- (ER) positive MCF-7, and ER-negative MDA-MB231 cells. Resveratrol is displaced from the purified integrin by an RGD, but not RGE, peptide, and by Vß3 integrin-specific Ab. Resveratrol action is blocked by siRNAß3, but not by siRNAV. [14C]-Resveratrol binds to commercially purified integrin Vß3 and to Vß3 prepared from MCF-7 cells; binding of [14C]-resveratrol to the ß3, but not to the V monomer, is displaced by unlabeled resveratrol. In conclusion, binding of resveratrol to integrin Vß3, principally to the ß3 monomer, is essential for transduction of the stilbene signal into p53-dependent apoptosis of breast cancer cells.—Lin, H.-Y., Lansing, L., Merillon, J.-M., Davis, F. B., Tang, H.-Y., Shih, A., Vitrac, X., Krisa, S., Keating, T., Cao, H. J., Bergh, J., Quackenbush, S., Davis, P. J. Integrin Vß3 contains a receptor site for resveratrol.
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