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

Research output: Contribution to journalArticle

109 Citations (Scopus)

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 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.

Original languageEnglish
JournalFASEB Journal
Volume20
Issue number10
DOIs
Publication statusPublished - Aug 2006
Externally publishedYes

Fingerprint

resveratrol
integrins
Integrins
receptors
apoptosis
Apoptosis
phosphotransferases (kinases)
Phosphotransferases
Cells
arginyl-glycyl-glutamic acid
Estrogen Receptors
breast neoplasms
Monomers
peptides
Breast Neoplasms
Stilbenes
Phosphorylation
antibodies
stilbenes
Antibodies

Keywords

  • Apoptosis
  • Breast cancer cell
  • Extracellular-regulated kinases 1 and 2
  • Integrin αVβ3
  • Resveratrol

ASJC Scopus subject areas

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

Cite this

Lin, H. Y., Lansing, L., Merillon, J. M., Davis, F. B., Tang, H. Y., Shih, A., ... Davis, P. J. (2006). Integrin αVβ3 contains a receptor site for resveratrol. FASEB Journal, 20(10). https://doi.org/10.1096/fj.06-5743fje

Integrin αVβ3 contains a receptor site for resveratrol. / Lin, Hung Yun; Lansing, Lawrence; Merillon, Jean Michel; Davis, Faith B.; Tang, Heng Yuan; Shih, Ai; Vitrac, Xavier; Krisa, Stephanie; Keating, Travis; Cao, H. James; Bergh, Joel; Quackenbush, Steven; Davis, Paul J.

In: FASEB Journal, Vol. 20, No. 10, 08.2006.

Research output: Contribution to journalArticle

Lin, HY, Lansing, L, Merillon, JM, Davis, FB, Tang, HY, Shih, A, Vitrac, X, Krisa, S, Keating, T, Cao, HJ, Bergh, J, Quackenbush, S & Davis, PJ 2006, 'Integrin αVβ3 contains a receptor site for resveratrol', FASEB Journal, vol. 20, no. 10. https://doi.org/10.1096/fj.06-5743fje
Lin HY, Lansing L, Merillon JM, Davis FB, Tang HY, Shih A et al. Integrin αVβ3 contains a receptor site for resveratrol. FASEB Journal. 2006 Aug;20(10). https://doi.org/10.1096/fj.06-5743fje
Lin, Hung Yun ; Lansing, Lawrence ; Merillon, Jean Michel ; Davis, Faith B. ; Tang, Heng Yuan ; Shih, Ai ; Vitrac, Xavier ; Krisa, Stephanie ; Keating, Travis ; Cao, H. James ; Bergh, Joel ; Quackenbush, Steven ; Davis, Paul J. / Integrin αVβ3 contains a receptor site for resveratrol. In: FASEB Journal. 2006 ; Vol. 20, No. 10.
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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 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.",
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AU - Vitrac, Xavier

AU - Krisa, Stephanie

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