title: Resveratrol at anti-angiogenesis/anticancer concentrations suppresses protein kinase G signaling and decreases IAPs expression in HUVECs.
abstract: BACKGROUND
  Resveratrol increases nitric oxide (NO) production via increased expression and activation of endothelial-form-NO-synthase (eNOS) in endothelial cells. However, the role of downstream cGMP/protein kinase G (PKG) signaling, a pathway activated by NO/eNOS, in pro- and anti-angiogenic effects of resveratrol is still unclear.
  
  
  METHODS
  Endogenous NO/cGMP/PKG pathway and downstream cell-survival proteins (Inhibitor of Apoptosis Proteins, IAPs) were studied in relation to pro- and anti-angiogenic effects of resveratrol in human umbilical vein endothelial cells (HUVECs).
  
  
  RESULTS
  Resveratrol at higher/anti-angiogenic concentrations inhibits HUVEC tube formation and cell migration/invasion (indices of angiogenesis). Resveratrol at lower concentrations stimulates proliferation and protects HUVECs against spontaneous apoptosis. 8-Br-cGMP, a direct activator of PKG, protects against pro-apoptotic effects of high-concentration resveratrol. Western blot analyses showed that anti-angiogenic concentrations of resveratrol suppress endogenous PKG kinase activity and decrease the expression of four cell-survival proteins, c-IAP1, c-IAP2, livin and XIAP.
  
  
  CONCLUSIONS
  Resveratrol-induced anti-angiogenesis/pro-apoptosis induced suppression of PKG signaling and decreased expression of the cell-survival proteins c-IAP1, c-IAP2, livin and XIAP.
authors.affiliation: Diabetes & Obesity Research Center, Alzheimer's & Parkinson's Disease Research Center, Cancer Research Center, Roseman Medical Education and Research Building at Summerlin Campus, Roseman University of Health Sciences, Las Vegas/Henderson, NV, U.S.A. Department of Chemistry, University of Nevada Las Vegas, Las Vegas, NV, U.S.A. Cancer Molecular Biology Section, Nevada Cancer Institute, Las Vegas, NV, U.S.A.
authors.forename: Janica C
authors.initials: JC
authors.lastname: Wong
authors.affiliation: Diabetes & Obesity Research Center, Alzheimer's & Parkinson's Disease Research Center, Cancer Research Center, Roseman Medical Education and Research Building at Summerlin Campus, Roseman University of Health Sciences, Las Vegas/Henderson, NV, U.S.A. College of Medicine and College of Pharmacy, Roseman University of Health Sciences, Henderson, NV, U.S.A. Cancer Molecular Biology Section, Nevada Cancer Institute, Las Vegas, NV, U.S.A. rfiscus@roseman.edu.
authors.forename: Ronald R
authors.initials: RR
authors.lastname: Fiscus
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D017209:Apoptosis; D002465:Cell Movement; D049109:Cell Proliferation; D002478:Cells, Cultured; D017869:Cyclic GMP-Dependent Protein Kinases / Q000235:genetics / Q000378:metabolism*; D004354:Drug Screening Assays, Antitumor; D015870:Gene Expression / Q000187:drug effects; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000235:genetics / Q000378:metabolism*; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D000077185:Resveratrol; D015398:Signal Transduction; D013267:Stilbenes / Q000494:pharmacology*
chemical_list: D020533:Angiogenesis Inhibitors; D051034:Inhibitor of Apoptosis Proteins; D007527:Isoenzymes; D013267:Stilbenes; D017869:Cyclic GMP-Dependent Protein Kinases; D000077185:Resveratrol
keywords: HUVECs; Inhibitor of Apoptosis Proteins (IAPs); Resveratrol; angiogenesis; protein kinase G (PKG)