Acacetin and Chrysin, Two Polyphenolic Compounds, Alleviate Telomeric Position Effect in Human Cells

Amina Boussouar (1) , Caroline Barette (2, 3) , Robert Nadon (4) , Adelaïde Saint-Léger (1) , Natacha Broucqsault (5) , Alexandre Ottaviani (1) , Arva Firozhoussen , Yiming Lu , Laurence Lafanechere (6) , Eric Gilson (1) , Frédérique Magdinier (1, 5) , Jing Ye (7)

1 LBMC - Laboratoire de Biologie Moléculaire de la Cellule
2 GPMS / CMBA - Groupe Plateforme et Moyens Scientifiques et techniques communs / Centre de Criblage pour Molécules Bio-Actives
3 GenChem - Genetics and Chemogenomics
4 Genome Quebec Innovation Center, Dept Human Genetics
5 GMGF - Génétique Médicale et Génomique Fonctionnelle
6 INSERM U823 - Institut d'oncologie/développement Albert Bonniot de Grenoble
7 GET - Géosciences Environnement Toulouse

We took advantage of the ability of human telomeres to silence neighboring genes (telomere position effect or TPE) to design a high-throughput screening assay for drugs altering telomeres. We identified, for the first time, that two dietary flavones, acacetin and chrysin, are able to specifically alleviate TPE in human cells. We further investigated their influence on telomere integrity and showed that both drugs drastically deprotect telomeres against DNA damage response. However, telomere deprotection triggered by shelterin dysfunction does not affect TPE, indicating that acacetin and chrysin target several functions of telomeres. These results show that TPE-based screening assays represent valuable methods to discover new compounds targeting telomeres.Molecular Therapy-Nucleic Acids (2013) 2, e116; doi:10.1038/mtna.2013.42; published online 20 August 2013.

Domaines: Biologie moléculaire; Biochimie [q-bio.BM]; Génomique, Transcriptomique et Protéomique [q-bio.GN]; Organisation et fonctions cellulaires [q-bio.SC]; Biotechnologies; Génétique humaine; Cardiologie et système cardiovasculaire; Neurobiologie

Amina Boussouar, Caroline Barette, Robert Nadon, Adelaïde Saint-Léger, Natacha Broucqsault, et al.. Acacetin and Chrysin, Two Polyphenolic Compounds, Alleviate Telomeric Position Effect in Human Cells. Molecular Therapy - Nucleic Acids, 2013, 2, pp.e116. ⟨10.1038/mtna.2013.42⟩. ⟨hal-01617538⟩