Dose-dependent effect of dehydroepiandrosterone, but not of its sulphate ester, on angiogenesis.

Abstract

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.

• Authors: Julia Varet, Loïc Vincent, Yvette Akwa, Pezhman Mirshahi, Agnès Lahary, Elizabeth Legrand, Paule Opolon, Zohair Mishal, Etienne-Emile Baulieu, Jeannette Soria, Claudine Soria, Hong Li
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 502 Issue 1-2 Pg. 21-30 (Oct 11 2004) ISSN: 0014-2999 [Print] Netherlands
• PMID: 15464086 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Angiogenesis Inhibitors
• Dehydroepiandrosterone
• Dehydroepiandrosterone Sulfate

Topics

• Angiogenesis Inhibitors (pharmacology)
• Cells, Cultured
• Dehydroepiandrosterone (pharmacology)
• Dehydroepiandrosterone Sulfate (pharmacology)
• Dose-Response Relationship, Drug
• Endothelial Cells (cytology, drug effects)
• Humans