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.
Varet
Julia
J
Laboratoire MERCI (Micro Environnement et Régulation Cellulaire Intégrée), Faculté de Médecine et Pharmacie, 76 Rouen, France.
Vincent
Loïc
L
Akwa
Yvette
Y
Mirshahi
Pezhman
P
Lahary
Agnès
A
Legrand
Elizabeth
E
Opolon
Paule
P
Mishal
Zohair
Z
Baulieu
Etienne-Emile
EE
Soria
Jeannette
J
Soria
Claudine
C
Li
Hong
H
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