INHIBITION OF ANGIOGENESIS AND BREAST-CANCER IN MICE BY THE MICROTUBULE INHIBITORS 2-METHOXYESTRADIOL AND TAXOL

2-Methoxyestradiol (2-ME), an endogenous estrogen metabolite which dis rupts microtubule function, has been shown to inhibit proliferating ce lls ill vitro and suppress certain murine tumors in vivo. In vitro scr eening has determined that breast cancer cell lines are most sensitive to inhibition by 2-ME, Additionally, 2-ME has been shown to inhibit a ngiogenesis in vitro, We tested whether 2-ME suppresses cytokine-induc ed angiogenesis ill vivo and inhibits growth of a human breast carcino ma in severe combined immunodeficient mice, A model of basic fibroblas t growth factor (bFGF) and vascular endothelial growth factor (VEGF)-i nduced corneal neovascularization in C57BL/6 mice was used to evaluate the antiangiogenic effects of 2-ME and other microtubule inhibitors s uch as Taxol, vincristine, and colchicine, 2-ME (150 mg/kg p.o., n = 2 0) inhibited bFGF and VEGF-induced neovascularization by 39% and 54%, respectively, Taxol (6 mg/kg i.p., n = 17) inhibited bFGF and VEGF-ind uced neovascularization by 45% and 37%, respectively, Vincristine (0.2 mg/kg i.p., n = 8) and colchicine (0.25 mg/kg i.p., n = 8) had no eff ect, Treatment with 2-ME (75 mg/kg p.o., n = 9) for 1 month suppressed the growth of a human breast carcinoma in mice by 60% without toxicit y, Recognition of the antiangiogenic and antitumor properties of 2-ME and Taxol may be crucial in planning clinical applications to angiogen esis-dependent diseases.