Angiogenesis inhibition by minocycline.

We describe a new inhibitor of angiogenesis, minocycline, a semisynthetic tetracycline antimicrobial with anticollagenase properties. Minocycline was incorporated into controlled release polymers and tested in the rabbit cornea against neovascularization in the presence of the VX2 carcinoma. Inhibition by minocycline was shown to be comparable to that of the combination of heparin and cortisone, a potent inhibitor of angiogenesis. Minocycline decreased tumor-induced angiogenesis by a factor of 4.5, 4.4, and 2.9 at 7, 14, and 21 days, respectively. At the end of the experiment, whereas the corneas with empty polymers had large, invasive, exophytic tumors, none of the corneas with minocycline had such vascular masses. Recently, studies of agents that disrupt collagen synthesis and deposition have yielded several new angiogenesis inhibitors. We suggest that investigation of agents that disrupt collagenolysis may similarly identify other angiogenesis inhibitors and further clarify the mechanisms of angiogenesis.