Integrin αVβ3 contains a receptor site for resveratrol

Hung Yun Lin, Lawrence Lansing, Jean Michel Merillon, Faith B. Davis, Heng Yuan Tang, Ai Shih, Xavier Vitrac, Stephanie Krisa, Travis Keating, H. James Cao, Joel Bergh, Steven Quackenbush, Paul J. Davis

研究成果: 雜誌貢獻文章

112 引文 斯高帕斯(Scopus)

摘要

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.
原文英語
期刊FASEB Journal
20
發行號10
DOIs
出版狀態已發佈 - 八月 2006
對外發佈Yes

ASJC Scopus subject areas

  • Agricultural and Biological Sciences (miscellaneous)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Biochemistry
  • Cell Biology

指紋 深入研究「Integrin αVβ3 contains a receptor site for resveratrol」主題。共同形成了獨特的指紋。

  • 引用此

    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