1. Integrin αVβ3 contains a receptor site for resveratrol
- Author
-
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, and Paul J. Davis
- Subjects
endocrine system diseases ,Integrin ,Estrogen receptor ,Resveratrol ,Biochemistry ,chemistry.chemical_compound ,Genetics ,Medicine ,skin and connective tissue diseases ,Receptor ,Molecular Biology ,biology ,Kinase ,business.industry ,organic chemicals ,food and beverages ,Cell biology ,Integrin alpha M ,chemistry ,Cancer cell ,biology.protein ,Cancer research ,Integrin, beta 6 ,business ,hormones, hormone substitutes, and hormone antagonists ,Biotechnology - 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 c...
- Published
- 2006
- Full Text
- View/download PDF