THE ENDOGENOUS ESTROGEN METABOLITE 2-METHOXYOESTRADIOL INHIBITS ANGIOGENESIS AND SUPPRESSES TUMOR-GROWTH

THE formation of new blood vessels (angiogenesis) is critical for the growth of tumours(1-3) and is; a dominant feature in various angiogeni c diseases such as diabetic retinopathy, arthritis, haemangiomas and p soriasis(4). Recognition of the potential therapeutic benefits of cont rolling pathological angiogenesis has led to a search for angiogenesis inhibitors. Here we report that 2-methoxyoestradiol, an endogenous oe strogen metabolite of previously unknown function, is a potent inhibit or of endothelial cell proliferation and migration as well as angiogen esis in vitro. Moreover, when administered orally in mice, it strongly inhibits the neovascularization of solid tumours and suppresses their growth. Unlike the angiostatic steroids of corticoid structure(5), it does not require the co-administration of heparin or sulphated cyclod extrins for activity. Thus, 2-methoxyoestradiol is the first steroid t o have high antiangiogenic activity by itself. Our results suggest tha t this compound may have therapeutic potential in cancer and other ang iogenic diseases.