Hammada scoparia flavonoids and rutin kill adherent and chemoresistant leukemic cells
2011
Bourogaa, Ezzeddine | Bertrand, Jessica | Despeaux, Mathieu | Jarraya, Raoudha | Fabre, Nicolas | Gamet-Payrastre, Laurence | Demur, Cécile | Fournié, Jean-Jacques | Damak, Mohamed | El Feki, Abdelfattah | Racaud-Sultan, Claire
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 GSK3 beta and inhibitors of GSK3 beta reproduced rutin-induced cytotoxicity. This study uncovers the potential of H. scoparia flavonoids and rutin to overcome CAM-DR in acute myeloid leukemia. (C) 2010 Elsevier Ltd. All rights reserved.
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