Bousseau 2019 FASEB J
|Bousseau S, Marchand M, Soleti R, Vergori L, Hilairet G, Recoquillon S, Le Mao M, Gueguen N, Khiati S, Clarion L, Bakalara N, Martinez MC, Germain S, Lenaers G, Andriantsitohaina R (2019) Phostine 3.1a as a pharmacological compound with antiangiogenic properties against diseases with excess vascularization. FASEB J [Epub ahead of print].|
Abstract: Angiogenesis is a complex process leading to the growth of new blood vessels from existing vasculature, triggered by local proangiogenic factors such as VEGF. An excess of angiogenesis is a recurrent feature of various pathologic conditions such as tumor growth. Phostines are a family of synthetic glycomimetic compounds that exhibit anticancer properties, and the lead compound 3-hydroxy-4,5-bis-benzyloxy-6-benzyloxymethyl-2-phenyl2-oxo-2λ5-[1,2]oxaphosphinane (PST 3.1a) shows antiglioblastoma properties both in vitro and in vivo. In the present study, we assessed the effect of PST 3.1a on angiogenesis and endothelial metabolism. In vitro, PST 3.1a (10 µM) inhibited all steps that regulate angiogenesis, including migration, proliferation, adhesion, and tube formation. In vivo, PST 3.1a reduced intersegmental vessel formation and vascularization of the subintestinal plexus in zebrafish embryos and also altered pathologic angiogenesis and glioblastoma progression in vivo. Mechanistically, PST 3.1a altered interaction of VEGF receptor 2 and glycosylation-regulating protein galectin-1, a key component regulating angiogenesis associated with tumor resistance. Thus, these data show that use of PST 3.1a is an innovative approach to target angiogenesis.
Labels: MiParea: Respiration Pathology: Cancer
Organism: Human Tissue;cell: Endothelial;epithelial;mesothelial cell Preparation: Intact cells
Coupling state: LEAK, ET Pathway: ROX HRR: Oxygraph-2k