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 mechanism of action is unknown, vascular collapse has been shown to precede tumor growth delay and regression. The aim of this study was to determine whether or not endothelial cell function was directly affected by clinically relevant concentrations of FAA. FAA at 100-250 micrograms/ml inhibited endothelial cell proliferation in vitro, but did not compromise cellular function or viability. FAA abolished tubule formation in an in vitro angiogenesis assay and reduced vascular development of the chick embryo chorioallantoic membrane. In addition to targeting established tumor vasculature, FAA may also affect proliferating endothelium which may be involved in mediating the reduced tumor growth rate or stasis often often observed after drug exposure. The chorioallantoic membrane of the chick embryo may represent an important model to elucidate more clearly the effect of FAA on a growing vascular network.
Lindsay
C K
CK
Tumor Biology and Carcinogenesis Section, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
Gomez
D E
DE
Thorgeirsson
U P
UP
D000482:Allantois / Q000098:blood supply; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D002642:Chick Embryo; D002823:Chorion / Q000098:blood supply; D003094:Collagen; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D004730:Endothelium, Vascular / Q000166:cytology* / Q000187:drug effects*; D005419:Flavonoids / Q000494:pharmacology*; D006801:Humans; D007797:Laminin; D008870:Microtubules / Q000187:drug effects; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D011509:Proteoglycans
D000970:Antineoplastic Agents; D004338:Drug Combinations; D005419:Flavonoids; D007797:Laminin; D011509:Proteoglycans; C059485:matrigel; C049328:flavone acetic acid; D003094:Collagen