SUPPRESSION OF ANGIOGENESIS BY THE ANTITUMOR AGENT TITANOCENE DICHLORIDE

Titanocene dichloride, which is an active antitumor agent against soli d but not blood-borne tumors, suppresses angiogenesis and inhibits bio synthesis of collagenous proteins in the in vivo system of the chorioa llantoic membrane of the chick embryo. The agent does not affect total protein biosynthesis in the same system. At non-toxic dose regimens t itanocene dichloride retards the growth of Walker 256 carcinosarcoma t ransplants in rats and reduces the number of seeded implants in the me senteric bed. At concentrations which suppress angiogenesis and inhibi t biosynthesis of collagenous proteins, the agent does not affect the viability of Walker 256 carcinosarcoma cells, or the attachment and pr oliferation of human A549 lung adenocarcinoma or human umbilical vein endothelial cells in culture. It appears that the antitumor activity o f titanocene dichloride may be attributed, at least in part, to its ab ility to suppress angiogenesis.