Flavone acetic acid induced changes in human endothelial permeability: potentiation by tumour-conditioned medium

Flavone acetic acid (FAA) causes significant regression of larger established tumours in murine in vivo systems. This in vivo effect of FAA has been shown to include a vascular component. In an effort to elucidate the mechanism of action of FAA, we have studied the effects of FAA on the permeability of human endothelium in vitro. Monolayers of human umbilical vein endothelial cells (HUVEC) grown on polycarbonate filters were incubated in 1 mg/ml FAA for 120 min at 37 degrees C. During the first 60 min, there was a 6-8-fold increase in permeability; this was followed by a return to control levels even in the continued presence of FAA. In contrast, in the presence of tumour conditioned medium, FAA caused a rapid 6-fold increase in permeability which did not subsequently return to control levels. The permeability changes which occurred under the latter conditions were accompanied by a rapid contraction of the cytoskeleton. The permeability of monolayers of human melanoma cells was unaffected by FAA.