Sanguinarine inhibits VEGF-induced angiogenesis in a fibrin gel matrix

Background: The identification of possible ways to block blood vessels formation has become a major scientific objective of the last decade and several phytochemicals are currently being exploited to target tumour angiogenesis. Aim: The effects of Sanguinarine (SA), an alkaloid from the root of Sanguinaria Canadensis, were evaluated in an in vitro angiogenesis model; moreover the effects on Akt phosphorylation in porcine aortic endothelial cell line (AOC) were also examined. Methods: SA (300 nM) was tested in the presence or absence of VEGF (100 ng/ml) in a three dimensional angiogenesis bioassay obtained pipetting a suspension of AOC on microcarrier beads in a fibrinogen solution before the addition of thrombine. Endothelial cell proliferation was measured at 48, 96, 144, 192 h. The phosphorylation of Akt was measured by ELISA in 2 x 105 AOC treated as described above. Results: The addition of SA abolished (p < 0.001) VEGF stimulatory effect on AOC growth at all the examined times. In addition, the stimutlatory effect induced by VEGF on Akt phosphorylation was significantly (p < 0.001) inhibited by SA. Conclusion: SA appear to be an antiangiogenic natural product by directly suppressing the proliferative effect of VEGF on endothelial cell line: this effect could be mediated by blocking the VEGF-induced Akt activation.