Flavone acetic acid as a modifier of endothelial cell function.

Area of Science:

• Oncology
• Immunology
• Pharmacology

Background:

• Flavone acetic acid (FAA) effectively reduces established tumors in vivo.
• The in vivo anti-tumor effect of FAA is hypothesized to be indirect, possibly immunological.
• Direct cytotoxicity of FAA to tumor and endothelial cells in vitro is minimal.

Purpose of the Study:

• To investigate the in vitro cytotoxicity of FAA on tumor and endothelial cells.
• To explore the in vivo sensitivity of tumors to FAA compared to in vitro cell sensitivity.
• To examine sublethal effects of FAA on endothelial cell function.

Main Methods:

• Assessing the survival of murine endothelial cells (B10) and fibrosarcoma cells (WHFIB) in vitro with FAA.
• Evaluating tumor growth delay in vivo after FAA administration.
• Investigating the impact of tumor-conditioned medium on FAA cytotoxicity.
• Studying the effects of FAA on human umbilical vein endothelial cell (HUVEC) permeability and procoagulant activity.

Main Results:

• FAA exhibited low cytotoxicity to B10 cells (63 hr for 0.1 survival) and WHFIB cells (>85 hr) in vitro.
• In vivo, WHFIB tumors were more sensitive to FAA than tumor cells in vitro, with a single dose causing a 10-day growth delay.
• FAA transiently increased HUVEC permeability and induced procoagulant activity, which was enhanced by a tumor cell factor.

Conclusions:

• FAA's in vivo anti-tumor efficacy is unlikely due to direct cytotoxicity.
• FAA may exert its effects by modulating endothelial cell function, increasing vascular permeability and procoagulant activity.
• Tumor-associated factors might potentiate FAA's effects on endothelial cells, contributing to in vivo tumor regression.