Effects of 15d-PGJ(2) on VEGF-induced angiogenic activities and expression of VEGF receptors in endothelial cells

Prostaglandins Other Lipid Mediat. 2006 May;79(3-4):230-44. doi: 10.1016/j.prostaglandins.2006.02.002. Epub 2006 Mar 31.

Abstract

15-Deoxy-Delta(12,14)-prostaglandin-J(2) (15d-PGJ(2)) upregulates expression of vascular endothelial growth factor (VEGF), but may inhibit angiogenesis. We found that 15d-PGJ(2) (1-10muM) attenuated all VEGF-induced angiogenic activities in human umbilical vein endothelial cells (HUVEC). It blocked almost completely cell proliferation, potently reduced migration, assembly into tube-like network on matrigel, and growth of capillaries into collagen gel. 15d-PGJ(2) inhibited expression of VEGFR-1 and VEGFR-2 receptors both at mRNA and protein levels. This inhibition, however, was transient (observed after 6-12h, but not after 24h) and weak (20-30%), and could not fully explain inhibition of response to VEGF. Accordingly, proliferation was inhibited when 15d-PGJ(2) was added 24h after VEGF or in cells stimulated with basic fibroblast growth factor. Interestingly, 15d-PGJ(2) decreased activities of c-jun and c-myc in HUVEC and overexpression of c-myc attenuated its antiproliferative effects. This suggests that inhibition of this transcription factor by 15d-PGJ(2) contributes to decrease in angiogenic response.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiogenesis Inducing Agents / antagonists & inhibitors*
  • Angiogenesis Inhibitors / pharmacology*
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Cells, Cultured
  • Dose-Response Relationship, Drug
  • Down-Regulation
  • Endothelial Cells / cytology
  • Endothelial Cells / drug effects
  • Endothelial Cells / metabolism*
  • Endothelium, Vascular / cytology
  • Endothelium, Vascular / metabolism*
  • Extracellular Signal-Regulated MAP Kinases / metabolism
  • Humans
  • Morphogenesis / drug effects
  • Prostaglandin D2 / analogs & derivatives*
  • Prostaglandin D2 / metabolism
  • Prostaglandin D2 / pharmacology
  • Proto-Oncogene Proteins c-myc / metabolism
  • RNA, Messenger / metabolism
  • Receptors, Vascular Endothelial Growth Factor / metabolism*
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Time Factors
  • Transcription Factors / metabolism
  • Umbilical Veins / cytology
  • Vascular Endothelial Growth Factor A / antagonists & inhibitors*

Substances

  • 15-deoxyprostaglandin J2
  • Angiogenesis Inducing Agents
  • Angiogenesis Inhibitors
  • MYC protein, human
  • Proto-Oncogene Proteins c-myc
  • RNA, Messenger
  • Recombinant Proteins
  • Transcription Factors
  • Vascular Endothelial Growth Factor A
  • Receptors, Vascular Endothelial Growth Factor
  • Extracellular Signal-Regulated MAP Kinases
  • Prostaglandin D2