CYTOSTATIC INHIBITION OF ENDOTHELIAL-CELL GROWTH BY THE ANGIOGENESIS INHIBITOR TNP-470 (AGM-1470)

Recently, me reported the anti-angiogenic action along with anti-tumou r activity of TNP-470 (AGM-1470). In this study, the effect of TNP-470 on the growth of human umbilical vein endothelial (HUVE) cells was ex amined. TNP-470 inhibited the growth of HUVE cells in a biphasic manne r. The inhibition was cytostatic in the first phase (complete inhibiti on at 300 pg ml(-1) with the IC50 of 15 pg ml(-1) and cytotoxic in the second phase (greater than or equal to 30 mu g ml(-1)). The cytostati c inhibition of HUVE cell growth by TNP-470 was durable after washing out TNP-470 in culture. Incorporation of thymidine but not uridine and leucine by HUVE cells was inhibited in the first phase, while that of all three compounds was inhibited in the second phase. Human and rat endothelial cells among various types of cells were the most sensitive to the cytostatic inhibition, while differences in the cytotoxic inhi bition were minimal. These results suggest that TNP-470 exerts its spe cific anti-angiogenic action by inhibiting cytostatically growth of en dothelial cells in a relatively specific manner.