EFFECT OF FLAVONE ACETIC-ACID ON ENDOTHELIAL-CELL PROLIFERATION - EVIDENCE FOR ANTIANGIOGENIC PROPERTIES

Flavone acetic acid (FAA) causes regression of a range of slow growing solid tumors implanted subcutaneously in mice. Although its precise m echanism of action is unknown, vascular collapse has been shown to pre cede tumor growth delay and regression. The aim of this study was to d etermine whether or not endothelial cell function was directly affecte d by clinically relevant concentrations of FAA. FAA at 100-250 mu g/ml inhibited endothelial cell proliferation in vitro, but did not compro mise cellular function or viability. FAA abolished tubule formation in an in vitro angiogenesis assay and reduced vascular development of th e chick embryo chorioallantoic membrane. In addition to targeting esta blished tumor vasculature, FAA may also affect proliferating endotheli um which may be involved in mediating the reduced tumor growth rate or stasis often observed after drug exposure. The chorioallantoic membra ne of the chick embryo may represent an important model to elucidate m ore clearly the effect of FAA on a growing vascular network.