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Sanguinarine inhibits VEGF‐induced angiogenesis in a fibrin gel matrix
Author(s) -
Basini Giuseppina,
Bussolati Simona,
Santini Sujen Eleonora,
Grasselli Francesca
Publication year - 2007
Publication title -
biofactors
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.204
H-Index - 94
eISSN - 1872-8081
pISSN - 0951-6433
DOI - 10.1002/biof.5520290102
Subject(s) - angiogenesis , sanguinarine , protein kinase b , phosphorylation , chemistry , pharmacology , endothelial stem cell , mmp2 , vascular endothelial growth factor , cell culture , in vitro , alkaloid , vegf receptors , microbiology and biotechnology , cancer research , biology , biochemistry , downregulation and upregulation , stereochemistry , genetics , gene
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 2×105 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 stimulatory 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.