AGM-1470 Inhibits the Growth of Human Glioblastoma Cells in Vitro and in Vivo

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Abstract
Glioblastoma is the most malignant primary brain tumor. Inhibition of angiogenesis is one potential strategy for treating this fatal hypervascular tumor. AGM-1470 (also called TNP-470), a novel, potent, fungus-derived inhibitor of angiogenesis, was tested on the growth of human glioblastoma cells in culture and on the growth of the tumor in nude mice. In nude mice with subrenally implanted U-87 MG glioblastomas, AGM-1470 significantly inhibited tumor growth (P < 0.01), and in nude mice with intracranial U-87 MG glioblastomas, AGM-1470 prolonged survival. In addition to its expected action as an angiogenesis inhibitor, AGM-1470 also directly inhibited U-87 MG cells in culture at concentrations similar to those that inhibited endothelial cells. The combined inhibition of glioblastoma cell mitosis and of glioblastoma-induced neovascularization suggests that AGM-1470 should be considered for further investigation in the treatment of this fatal tumor.