PUBLICATION
Phostine 3.1a as a pharmacological compound with antiangiogenic properties against diseases with excess vascularization
- Authors
- Bousseau, S., Marchand, M., Soleti, R., Vergori, L., Hilairet, G., Recoquillon, S., Le Mao, M., Gueguen, N., Khiati, S., Clarion, L., Bakalara, N., Martinez, M.C., Germain, S., Lenaers, G., Andriantsitohaina, R.
- ID
- ZDB-PUB-190301-8
- Date
- 2019
- Source
- FASEB journal : official publication of the Federation of American Societies for Experimental Biology 33(5): 5864-5875 (Journal)
- Registered Authors
- Keywords
- angiogenesis, cancer growth, endothelial metabolism, glycosylation, pharmacotherapy
- MeSH Terms
-
- Adenosine Diphosphate/metabolism
- Adenosine Triphosphate/metabolism
- Angiogenesis Inhibitors/pharmacology*
- Animals
- Apoptosis
- Cell Adhesion
- Cell Line, Tumor
- Cell Movement/drug effects
- Cell Proliferation
- Endothelial Cells/metabolism
- Extracellular Matrix/metabolism
- Galectin 1/metabolism
- Glioblastoma/metabolism
- Glycosylation
- Human Umbilical Vein Endothelial Cells
- Humans
- Male
- Mice
- Mice, Nude
- Neoplasm Transplantation
- Neovascularization, Pathologic/drug therapy*
- Phosphines/pharmacology*
- Signal Transduction/drug effects
- Vascular Endothelial Growth Factor A/metabolism
- Vascular Endothelial Growth Factor Receptor-2/metabolism
- Zebrafish
- PubMed
- 30817178 Full text @ FASEB J.
Citation
Bousseau, S., Marchand, M., Soleti, R., Vergori, L., Hilairet, G., Recoquillon, S., Le Mao, M., Gueguen, N., Khiati, S., Clarion, L., Bakalara, N., Martinez, M.C., Germain, S., Lenaers, G., Andriantsitohaina, R. (2019) Phostine 3.1a as a pharmacological compound with antiangiogenic properties against diseases with excess vascularization. FASEB journal : official publication of the Federation of American Societies for Experimental Biology. 33(5):5864-5875.
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.-Bousseau, S., Marchand, M., Soleti, R., Vergori, L., Hilairet, G., Recoquillon, S., Le Mao, M., Gueguen, N., Khiati, S., Clarion, L., Bakalara, N., Martinez, M. C., Germain, S., Lenaers, G., Andriantsitohaina, R. Phostine 3.1a as a pharmacological compound with antiangiogenic properties against diseases with excess vascularization.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping