SUPPRESSION OF CYCLIN D1 MESSENGER-RNA EXPRESSION BY THE ANGIOGENESIS INHIBITOR TNP-470 (AGM-1470) IN VASCULAR CELLS ENDOTHELIAL

The effects of TNP-470 on DNA synthesis and the expression of c-myc and cyclin D1 mRNAs were investigated in human umbilical vein endothelial (HUVE) cells synchronized by serum depletion and stimulated with bFGF and serum. DNA synthesis occurring 16 h after stimulation was inhibited when TNP-470 was present from 2 to 6 h after stimulation. C-myc mRNA expression occurring 2 h after stimulation was not inhibited by the addition of TNP-470. Cyclin D1 mRNA expression occurring 6 h after stimulation was suppressed in the presence of TNP-470 from 2 to 6 h after stimulation. On the other hand, cyclin D1 expression was not suppressed in the TNP-470-insensitive human tumor cell line WiDr. These results suggest that the inhibition of HUVE cells by TNP-470 is due to the suppression of cyclin D1 expression in mid G(1) phase. (C) 1994 Academic Press, Inc.