Scientific conference in universities or research centers (Scientific conferences in universities or research centers)
Understanding angiogenesis through novel epigenetic modulators
Shiva Shankar, Thammadihalli Veerasangaiah; Sulka, Béatrice; Blacher, Silvia et al.
2012
 

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Abstract :
[en] DNA methylation and histone deacetylation are two key epigenetic modifications that play central role in regulation of gene expression. Several studies have shown that histone deacetylases (HDAC) and DNA methyltransferases (DNMT) inhibitors are potent anti-angiogenic compounds. Though combination of HDAC and DNMT inhibitors are now being examined in clinical trials of hematological malignancies, little work has been done to understand the effect of this combination on physiological and tumoral angiogenesis. We have designed and tested a family of twin drugs with intrinsic HDAC and DNMT inhibitory activities in relevant models of angiogenesis in vitro (Human Umbilical Vein Endothelial Cells – HUVEC and aortic ring) and in vivo (chick chorioallantoic membrane and Zebrafish). We have identified a lead compound having quantifiable anti-angiogenic effect without cytotoxicity affecting global histone acetylation and DNA methylation levels. In order to elucidate its anti-angiogenic mechanism, we characterized gene expression pattern simultaneously with the methylation profile of HUVEC cells treated with the lead compound and reference epigenetic modulators. This approach based on parallel microarray analyses permitted us to underscore a list of genes exclusively affected by the lead compound but not by other HDAC or DNMT inhibitors. These genes were then analyzed using the Ingenuity Pathway software revealing potential involvement of a subset of genes in angiogenesis. Our present work is focused on exploring the exact role of these genes on angiogenesis using RNA silencing and vectors cloned with genes of interest. We are using these novel epigenetic modulators as a tool to understand the regulatory mechanism of angiogenesis and to develop effective approaches to treat cancer.
Disciplines :
Biotechnology
Author, co-author :
Shiva Shankar, Thammadihalli Veerasangaiah ;  Université de Liège - ULiège > Form. doct. sc. agro. & ingé. biol.
Sulka, Béatrice
Blacher, Silvia ;  Université de Liège - ULiège > Département des sciences cliniques > Labo de biologie des tumeurs et du développement
Maillard, Catherine ;  Université de Liège - ULiège > Département des sciences cliniques > Labo de biologie des tumeurs et du développement
Noël, Agnès ;  Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Biologie cellulaire et moléculaire appliquée à l'homme
Pendeville-Samain, Hélène 
Lambert, Didier
Wouters, Johan
Willems, Luc  ;  Université de Liège - ULiège > Chimie et bio-industries > Biologie cell. et moléc.
Language :
English
Title :
Understanding angiogenesis through novel epigenetic modulators
Publication date :
22 June 2012
Event name :
GIGA Cancer Day
Event organizer :
EDT
Event place :
Liege, Belgium
Event date :
22-06-12
Available on ORBi :
since 08 August 2012

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