Suppression of angiogenesis by the antitumor agent titanocene dichloride.

Titanocene dichloride, which is an active antitumor agent against solid but not blood-borne tumors, suppresses angiogenesis and inhibits biosynthesis of collagenous proteins in the in vivo system of the chorioallantoic membrane of the chick embryo. The agent does not affect total protein biosynthesis in the same system. At non-toxic dose regimens titanocene dichloride retards the growth of Walker 256 carcinosarcoma transplants in rats and reduces the number of seeded implants in the mesenteric bed. At concentrations which suppress angiogenesis and inhibit biosynthesis of collagenous proteins, the agent does not affect the viability of Walker 256 carcinosarcoma cells, or the attachment and proliferation of human A549 lung adenocarcinoma or human umbilical vein endothelial cells in culture. It appears that the antitumor activity of titanocene dichloride may be attributed, at least in part, to its ability to suppress angiogenesis.