Suppression of cyclin D1 mRNA expression by the angiogenesis inhibitor TNP-470 (AGM-1470) in vascular endothelial cells.
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 G1 phase.
Pharmaceutical Research Laboratories III, Takeda Chemical Industries Ltd., Osaka, Japan.
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Hori
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Ikeyama
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Sudo
D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D001483:Base Sequence; D002478:Cells, Cultured; D016895:Culture Media, Serum-Free; D019938:Cyclin D1; D016213:Cyclins / Q000096:biosynthesis*; D003510:Cyclohexanes; D017931:DNA Primers; D004261:DNA Replication / Q000187:drug effects; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism*; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects*; D016259:Genes, myc / Q000187:drug effects; D006801:Humans; D007700:Kinetics; D008969:Molecular Sequence Data; D000077609:O-(Chloroacetylcarbamoyl)fumagillol; D015345:Oligonucleotide Probes; D015513:Oncogene Proteins / Q000096:biosynthesis*; D016133:Polymerase Chain Reaction; D016271:Proto-Oncogene Proteins c-myc / Q000096:biosynthesis; D012333:RNA, Messenger / Q000096:biosynthesis; D012717:Sesquiterpenes / Q000494:pharmacology*; D013489:Suppression, Genetic; D013997:Time Factors; D014471:Umbilical Veins
D000903:Antibiotics, Antineoplastic; D016895:Culture Media, Serum-Free; D016213:Cyclins; D003510:Cyclohexanes; D017931:DNA Primers; D015345:Oligonucleotide Probes; D015513:Oncogene Proteins; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger; D012717:Sesquiterpenes; D016222:Fibroblast Growth Factor 2; D019938:Cyclin D1; D000077609:O-(Chloroacetylcarbamoyl)fumagillol