isocoumarin-nm-3 and Breast-Neoplasms

Antiangiogenic therapy, although effective in shrinking tumors, has not yet been established as a standalone treatment for cancer. This therapeutic limitation can be overcome by combining angiogenesis inhibitors with chemotherapeutic agents. NM-3, a small molecule isocoumarin, is a recently discovered angiogenesis inhibitor. Here we demonstrate that NM-3 inhibits the proliferation of human umbilical vein endothelial cells in vitro, at concentrations 10-fold less than those required to inhibit normal fibroblasts or tumor cells (HT29, MKN28, and MCF-7). NM-3 alone inhibits endothelial sprouting and tube formation in vitro. The results also show that synergistic antiproliferative activity is observed when human umbilical vein endothelial cells are treated with NM-3 in combination with 5-fluorouracil. The effects of treatment with NM-3 and various chemotherapeutic agents were also evaluated in tumor xenografts. The results demonstrate that combined treatment with NM-3 and chemotherapeutic agents significantly reduced mean tumor volume compared with either treatment alone, with no effects on body weight changes. Taken together, these findings demonstrate that NM-3 is a well-tolerated angiogenesis inhibitor that significantly increases the efficacy of existing antineoplastic agents.

Topics: Angiogenesis Inhibitors; Animals; Antineoplastic Agents; Aorta; Breast Neoplasms; Cell Movement; Coumarins; Cyclophosphamide; Drug Synergism; Endothelium, Vascular; Female; Fluorouracil; Growth Inhibitors; Humans; Isocoumarins; Male; Mice; Mice, Nude; Neovascularization, Pathologic; Paclitaxel; Prostatic Neoplasms; Rats; Rats, Sprague-Dawley; Xenograft Model Antitumor Assays