Effects of danazol on endothelial cell function and angiogenesis.
OBJECTIVE
To determine the effects of the androgen-like synthetic steroid, danazol, on endothelial cell function and angiogenesis.


METHODS
In vitro cell culture models were designed to investigate three critical steps involved in angiogenesis: endothelial cell proliferation, invasion, and tube formation.


METHODS
Research laboratory at a level one trauma center.


METHODS
Commercially available human umbilical vein endothelial cells (HUVEC) were purchased from a pooled patient source.


METHODS
The HUVEC cells were treated with danazol at concentrations ranging from 1 to 100 microM and evaluated using a series of angiogenesis assays.


METHODS
Absolute cells numbers were quantified using colorimetric methods and fluorescent dyes for cells exposed to danazol in both proliferation assays and invasion chambers. AngiQuant vl.33 software was used to evaluate the formation of capillary-like structures on extracellular matrix gels in the presence of danazol.


RESULTS
Endothelial cells scrutinized by our in vitro models exhibited decreased proliferation (up to 86%) and tube length (up to 115%) in the presence danazol. Cellular invasion through extracellular matrix, however, was not apparently affected by danazol under the conditions used.


CONCLUSIONS
Danazol interfered with two of the three steps of angiogenesis studied in vitro. This data may help elucidate the mode of action for danazol in vivo.
Thomas
Gregory W
GW
DMI Biosciences Inc., Aurora, Colorado, USA.
Rael
Leonard T
LT
Shimonkevitz
Rick
R
Curtis
C Gerald
CG
Bar-Or
Raphael
R
Bar-Or
David
D
D020533:Angiogenesis Inhibitors / Q000494:pharmacology; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D003613:Danazol / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000187:drug effects* / Q000502:physiology*; D006801:Humans; D018919:Neovascularization, Physiologic / Q000187:drug effects* / Q000502:physiology
D020533:Angiogenesis Inhibitors; D003613:Danazol