Inhibitory effect of theobromine on induction of angiogenesis and VEGF mRNA expression in v-raf transfectants of human urothelial cells HCV-29.
Neovascularisation plays a crucial role in solid tumor growth and metastasis formation. Our previous studies showed that theophylline and theobromine suppressed cutaneous neovascular reaction induced in mice by human blood leukocytes, and lung as well as ovarian cancer cells. Here, we investigated the in vivo effect of theobromine on angiogenic activity of human urothelial cell line HCV-29, v-raf transfected (mouse cutaneous assay), and the in vitro effect of this drug on VEGF, tPA, uPA and PAI mRNA expression in these cells (RT-PCR method). Theobromine suppressed angiogenesis induced in mice by HCV-29-v-raf cells, inhibited VEGF mRNA expression, and had no effect on transcription of uPA and tPA in these cells. HCV-29-v-raf transfectants do not display transcripts of PAI, in the presence or the absence of theobromine.
Skopinska-Rózewska
E
E
Department of Immunology, National Institute of Tuberculosis and Lung Diseases, Warsaw, Poland.
Janik
P
P
Przybyszewska
M
M
Sommer
E
E
Bialas-Chromiec
B
B
D000818:Animals; D002460:Cell Line; D016228:Endothelial Growth Factors / Q000235:genetics* / Q000494:pharmacology; D005260:Female; D006801:Humans; D008222:Lymphokines / Q000235:genetics* / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D027384:Oncogene Proteins v-raf; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics; D012333:RNA, Messenger; D015682:Retroviridae Proteins, Oncogenic / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013805:Theobromine / Q000494:pharmacology*; D010959:Tissue Plasminogen Activator / Q000187:drug effects / Q000235:genetics; D014162:Transfection; D014568:Urokinase-Type Plasminogen Activator / Q000187:drug effects / Q000235:genetics; D019459:Urothelium / Q000166:cytology / Q000187:drug effects*; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D014665:Vasodilator Agents / Q000494:pharmacology
D016228:Endothelial Growth Factors; D008222:Lymphokines; D017395:Plasminogen Activator Inhibitor 1; D012333:RNA, Messenger; D015682:Retroviridae Proteins, Oncogenic; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D014665:Vasodilator Agents; D027384:Oncogene Proteins v-raf; D010959:Tissue Plasminogen Activator; D014568:Urokinase-Type Plasminogen Activator; D013805:Theobromine