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 αVβ3 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 αVβ3, but not to αVβ5, inhibits activation by resveratrol of ERK1/2 and p53 and consequent apoptosis in estrogen receptor-α (ERα) positive MCF-7, and ERα-negative MDA-MB231 cells. Resveratrol is displaced from the purified integrin by an RGD, but not RGE, peptide, and by αVβ3 integrin-specific Ab. Resveratrol action is blocked by siRNAβ3, but not by siRNAαV. [ 14C]-Resveratrol binds to commercially purified integrin αVβ3 and to αVβ3 prepared from MCF-7 cells; binding of [ 14C]-resveratrol to the β3, but not to the αV monomer, is displaced by unlabeled resveratrol. In conclusion, binding of resveratrol to integrin αVβ3, principally to the β3 monomer, is essential for transduction of the stilbene signal into p53-dependent apoptosis of breast cancer cells.
ASJC Scopus subject areas
- Agricultural and Biological Sciences (miscellaneous)
- Biochemistry, Genetics and Molecular Biology(all)
- Cell Biology
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. (2006). Integrin αVβ3 contains a receptor site for resveratrol. FASEB Journal, 20(10). https://doi.org/10.1096/fj.06-5743fje