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Hammada scoparia flavonoids and rutin kill adherent and chemoresistant leukemic cells |
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| Authors: | Bourogaa Ezzeddine Bertrand Jessica Despeaux Mathieu Jarraya Raoudha Fabre Nicolas Payrastre Laurence Demur Cécile Fournié Jean-Jacques Damak Mohamed Feki Abdelfattah El Racaud-Sultan Claire |
| Affiliation: | a INSERM, U563, Université Toulouse III Paul Sabatier, Centre de Physiopathologie de Toulouse Purpan, Toulouse, France b Laboratoire d’Hématologie, CHU Toulouse, Hôpital Purpan, Toulouse, France c Laboratoire de Chimie des Substances Naturelles, Sfax, Tunisia d Laboratoire d’Ecophysiologie Animale, Sfax, Tunisia e Laboratoire de pharmacochimie des substances naturelles et pharmacophores redox, Université de Toulouse, UPS, UMR 152, Toulouse, France f UMR 1089 Xénobiotiques, ENVT/Inra, PA3S, Toulouse, France |
| 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. |
| Keywords: | Flavonoids GSK3β Leukemia Cell adhesion Drug resistance |
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