Dose-dependent effect of dehydroepiandrosterone, but not of its sulphate ester, on angiogenesis.
Although dehydroepiandrosterone (DHEA) is widely used in the elderly to prevent some adverse effects of ageing, possible deleterious side effects have not been fully assessed. We evaluated the direct actions of DHEA and DHEA sulphate on angiogenesis, a critical event in pathologies that are common in the elderly (cancer, atherosclerosis, inflammation... etc.). At physiological concentrations found in human plasma following DHEA therapy (1-50 nM), DHEA had no action on angiogenesis in vitro. In contrast, higher concentrations of DHEA (10-100 microM), which can be found in tissues after local administration or storage, inhibited in vitro endothelial cell proliferation (blockage in G2/M), migration and capillary tube formation and in vivo angiogenesis in the Matrigel plug assay. This inhibition might be due to a decreased glucose-6-phosphate dehydrogenase activity and to a modification of the tubulin network involved in cell proliferation and migration. The sulphate ester form of DHEA had no effect on angiogenesis.
Laboratoire MERCI (Micro Environnement et Régulation Cellulaire Intégrée), Faculté de Médecine et Pharmacie, 76 Rouen, France.
Julia
J
Varet
Loïc
L
Vincent
Yvette
Y
Akwa
Pezhman
P
Mirshahi
Agnès
A
Lahary
Elizabeth
E
Legrand
Paule
P
Opolon
Zohair
Z
Mishal
Etienne-Emile
EE
Baulieu
Jeannette
J
Soria
Claudine
C
Soria
Hong
H
Li
D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D002478:Cells, Cultured; D003687:Dehydroepiandrosterone / Q000494:pharmacology*; D019314:Dehydroepiandrosterone Sulfate / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects*; D006801:Humans
D020533:Angiogenesis Inhibitors; D003687:Dehydroepiandrosterone; D019314:Dehydroepiandrosterone Sulfate