CLARITHROMYCIN IS A POTENT INHIBITOR OF TUMOR-INDUCED ANGIOGENESIS

We investigated the inhibitory effect of clarithromycin, a 14-membered ring macrolide antibiotic, on tumor-induced angiogenesis in vivo usin g a mouse dorsal air sac model. The inhibitory effect of clarithromyci n was dose-dependent, and 100 mg/kg of clarithromycin administered int raperitoneally twice a day reduced the area of dense capillary network to about 30% that of the control. However, in concentrations up to 50 mu M clarithromycin had no effect on lung cancer cells and human vasc ular endothelial cell growth, endothelial cell migration, or lung canc er cell production of the angiogenesis-inducing factors interleukin-8 and vascular endothelial growth factor. Clarithromycin in concentratio ns greater than 10 mu M inhibited endothelial cell tube formation on M atrigel in a dose-dependent manner. These data suggest clarithromycin is a potent inhibitor of tumor-induced angiogenesis that exerts its ef fect by inhibiting endothelial cell tube formation, and may be a possi ble candidate for therapeutic application.