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.


OBJECTIVE
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 10(5) 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.


CONCLUSIONS
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.
Basini
Giuseppina
G
Dipartimento di Produzioni Animali, Biotecnologie Veterinarie, Qualità e Sicurezza degli Alimenti, Sezione di Fisiologia Veterinaria, Università di Parma, Parma, Italy. basini@unipr.it
Bussolati
Simona
S
Santini
Sujen Eleonora
SE
Grasselli
Francesca
F
D000470:Alkaloids / Q000494:pharmacology*; D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D001011:Aorta / Q000166:cytology; D053119:Benzophenanthridines / Q000494:pharmacology*; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D005337:Fibrin / Q000737:chemistry; D005782:Gels; D007546:Isoquinolines / Q000494:pharmacology*; D008858:Microscopy, Phase-Contrast; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D010766:Phosphorylation / Q000187:drug effects; D018517:Plant Roots / Q000737:chemistry; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D031681:Sanguinaria / Q000737:chemistry; D013552:Swine; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology*
D000470:Alkaloids; D020533:Angiogenesis Inhibitors; D053119:Benzophenanthridines; D005782:Gels; D007546:Isoquinolines; D042461:Vascular Endothelial Growth Factor A; D005337:Fibrin; C005705:sanguinarine; D051057:Proto-Oncogene Proteins c-akt