title: Hammada scoparia flavonoids and rutin kill adherent and chemoresistant leukemic cells.
abstract: In search for compounds able to reduce cell adhesion-mediated drug resistance (CAM-DR), we studied effects of Hammada scoparia extracts on leukemic cells adherent or in suspension. We show that H. scoparia flavonoidic fraction and its compound rutin induce apoptosis specifically in adherent leukemic cells and abolish CAM-DR. Importantly, rutin inhibited survival of adherent leukemic progenitors (CD34(+)38(-)123(+)) but spared normal progenitors (CD34(+)38(-)). The pro-apoptotic effects of rutin were correlated with a decrease of active GSK3β and inhibitors of GSK3β reproduced rutin-induced cytotoxicity. This study uncovers the potential of H. scoparia flavonoids and rutin to overcome CAM-DR in acute myeloid leukemia.
authors.affiliation: Laboratoire de Chimie des Substances Naturelles, Sfax, Tunisia.
authors.forename: Ezzeddine
authors.initials: E
authors.lastname: Bourogaa
authors.forename: Jessica
authors.initials: J
authors.lastname: Bertrand
authors.forename: Mathieu
authors.initials: M
authors.lastname: Despeaux
authors.forename: Raoudha
authors.initials: R
authors.lastname: Jarraya
authors.forename: Nicolas
authors.initials: N
authors.lastname: Fabre
authors.forename: Laurence
authors.initials: L
authors.lastname: Payrastre
authors.forename: Cécile
authors.initials: C
authors.lastname: Demur
authors.forename: Jean-Jacques
authors.initials: JJ
authors.lastname: Fournié
authors.forename: Mohamed
authors.initials: M
authors.lastname: Damak
authors.forename: Abdelfattah El
authors.initials: AE
authors.lastname: Feki
authors.forename: Claire
authors.initials: C
authors.lastname: Racaud-Sultan
mesh_terms: D018952:Antigens, CD34 / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D002448:Cell Adhesion / Q000187:drug effects*; D002478:Cells, Cultured; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D005419:Flavonoids / Q000494:pharmacology; D005434:Flow Cytometry; D038362:Glycogen Synthase Kinase 3 / Q000037:antagonists & inhibitors / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D006412:Hematopoietic Stem Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000473:pathology*; D008517:Phytotherapy; D012431:Rutin / Q000494:pharmacology*; D036721:Scoparia / Q000737:chemistry*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
chemical_list: D018952:Antigens, CD34; D005419:Flavonoids; D012431:Rutin; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; D038362:Glycogen Synthase Kinase 3