RA-VII, a cyclic hexapeptide isolated from Rubiae radix, binds to actin, causing a conformational change in the actin molecule and inducing G2 arrest by inhibiting cytokinesis. Here we examined the effect of
RA-VII, its water-soluble derivative, and related RA-III and
RA-V on endothelial cells. Among the four compounds tested,
RA-VII most potently inhibited angiogenesis-related properties of endothelial cells (i.e. migration and proliferation) in vitro. We confirmed the anti-angiogenic activity of
RA-VII in vivo by using a mouse corneal model. We then applied
RA-VII for the treatment of
tumors in mice. Daily
intraperitoneal injection of
RA-VII (1.5 or 3 mg/kg/day) exhibited no toxic effect on the animals, but significantly and dose dependently inhibited the growth of
Lewis lung carcinoma cells previously inoculated into the mice. Interestingly, although two doses of
RA-VII decreased the
tumor vascular area to a similar extent, a higher dose of
RA-VII led to
tumor vessel maturation together with a significant increase in
tumor cell apoptosis. Also,
RA-VII showed a cytotoxic effect on
Lewis lung carcinoma cells. These results indicate that metronomic scheduling of
RA-VII is efficient for
cancer treatment. A careful dose setting of
RA-VII is crucial to obtain therapeutic superiority, possibly through
tumor vessel maturation and a better distribution of the compound in the
tumor tissue.