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Effect of flavone acetic acid on endothelial cell proliferation: evidence for antiangiogenic properties
C K Lindsay1, D E Gomez, U P Thorgeirsson
1Tumor Biology and Carcinogenesis Section, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
Abstract:
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.
Insights
Flavone acetic acid (FAA) inhibits endothelial cell proliferation and angiogenesis, suggesting it may impact tumor vascular development. This study investigates FAA
Area of Science:
- Oncology
- Vascular Biology
- Pharmacology
Background:
- Flavone acetic acid (FAA) is known to induce regression of slow-growing solid tumors in mice.
- Tumor regression is preceded by vascular collapse, but the precise mechanism of FAA action remains unclear.
- This study investigates the direct effects of FAA on endothelial cells.
Purpose of the Study:
- To determine if clinically relevant concentrations of FAA directly affect endothelial cell function.
- To elucidate the anti-angiogenic properties of FAA.
- To explore the potential of the chick embryo chorioallantoic membrane as a model for studying FAA's effects on vascular networks.
Main Methods:
- In vitro assessment of endothelial cell proliferation, function, and viability exposed to FAA.
- In vitro angiogenesis assay to evaluate tubule formation.
- Chick embryo chorioallantoic membrane assay to assess vascular development.
Main Results:
- FAA (100-250 µg/ml) inhibited endothelial cell proliferation in vitro without compromising cell viability or function.
- FAA abolished in vitro tubule formation, a key step in angiogenesis.
- FAA reduced vascular development in the chick embryo chorioallantoic membrane model.
Conclusions:
- FAA exhibits direct anti-proliferative and anti-angiogenic effects on endothelial cells.
- FAA may target both established tumor vasculature and proliferating endothelium, contributing to tumor growth delay.
- The chick embryo chorioallantoic membrane is a valuable model for further investigation of FAA's vascular effects.