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 metastasi s formation. Our previous studies showed that theophylline and theobromine suppressed cutaneous neovascular reaction induced in mice by human blood le ukocytes, and lung as well as ovarian cancer cells. Here, we investigated t he in vivo effect of theobromine on angiogenic activity of human urothelial cell line HCV-29, v-raf transfected (mouse cutaneous assay), and the in vi tro 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 theobrom ine.