Reference : Histone deacetylases inhibitors as anti-angiogenic agents altering vascular endotheli...
Scientific journals : Article
Human health sciences : Oncology
Life sciences : Biochemistry, biophysics & molecular biology
http://hdl.handle.net/2268/24081
Histone deacetylases inhibitors as anti-angiogenic agents altering vascular endothelial growth factor signaling
English
Deroanne, Christophe mailto [Université de Liège - ULg > Département des sciences biomédicales et précliniques > Protéines et glycoprot. de matr.extracell. et membran.basal. >]
Bonjean, Karine [> > > >]
Servotte, Sandrine [> > > >]
Devy, Laetitia [> > > >]
Colige, Alain mailto [Université de Liège - ULg > Département des sciences biomédicales et précliniques > Protéines et glycoprot. de matr.extracell. et membran.basal. >]
Clausse, Nathalie [> > > >]
Blacher, Silvia mailto [Université de Liège - ULg > Département des sciences cliniques > Labo de biologie des tumeurs et du développement >]
Verdin, Eric [ > > ]
Foidart, Jean-Michel mailto [Université de Liège - ULg > Département des sciences cliniques > Gynécologie - Obstétrique >]
Nusgens, Betty mailto [Université de Liège - ULg > Département des sciences biomédicales et précliniques > Département des sciences biomédicales et précliniques >]
Castronovo, Vincenzo mailto [Université de Liège - ULg > Département des sciences biomédicales et précliniques > Biologie générale et cellulaire >]
17-Jan-2002
Oncogene
Nature Publishing Group
21
3
427-436
Yes (verified by ORBi)
International
0950-9232
London
[en] angiogenesis ; trichostatin A ; suberoylanilide hydroxamic acid ; VEGF ; neuropilin-1 ; semaphorin III
[en] Angiogenesis is a complex biological process involving the coordinated modulation of many genes. Histone deacetylases (HDAC) are a growing family of enzymes that mediate the availability of chromatin to the transcriptional machinery. Trichostatin-A (TSA) and suberoylanilide hydroxamic acid (SAHA), two HDAC inhibitors known to relieve gene silencing, were evaluated as potential antiangiogenic agents. TSA and SAHA were shown to prevent vascular endothelial growth factor (VEGF)-stimulated human umbilical cord endothelial cells (HUVEC) from invading a type I collagen gel and forming capillary-like structures. SAHA and TSA inhibited the VEGF-induced formation of a CD31-positive capillary-like network in embryoid bodies and inhibited the VEGF-induced angiogenesis in the CAM assay. TSA also prevented, in a dose-response relationship, the sprouting of capillaries from rat aortic rings. TSA inhibited in a dose-dependent and reversible fashion the VEGF-induced expression of VEGF receptors, VEGFR1, VEGFR2, and neuropilin-1. TSA and SAHA upregulated the expression by HUVEC of semaphorin III, a recently described VEGF competitor, at both mRNA and protein levels. This effect was specific to endothelial cells and was not observed in human fibroblasts neither in vascular smooth muscle cells. These observations provide a conspicuous demonstration that HDAC inhibitors are potent anti-angiogenic factors altering VEGF signaling.
Fonds de la Recherche Scientifique (Communauté française de Belgique) - F.R.S.-FNRS ; Centre Anticancéreux près l'Université de Liège ; TELEVIE
http://hdl.handle.net/2268/24081

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