[en] Defect in apoptosis has been implicated as a major cause of resistance to chemotherapy observed in B cell chronic lymphocytic leukaemia (B CLL). This study evaluated the pro-apoptotic effect of an anthocyanin-rich dietary bilberry extract (Antho 50) on B CLL cells from 30 patients and on peripheral blood mononuclear cells (PBMCs) from healthy subjects, and determined the underlying mechanism. Antho 50 induced concentration- and time-dependent pro-apoptotic effects in B CLL cells isolated from patients but little or no effect in PBMCs. Among the main phenolic compounds present in this bilberry extract, delphinidin-3-O-glucoside and delphinidin-3-O-rutinoside showed the highest apoptotic effect on B CLL cells, suggesting that anthocyanins play a main role in the cytotoxic activity. Antho 50-induced apoptosis is associated with activation of caspase 3 and down-regulation of the anti-apoptotic protein UHRF1. Antho 50 induced also rapid dephosphorylation of Akt and Bad, and down-regulation of Bcl-2 resulting in reduced cell viability. Antho 50 significantly induced PEG-catalase-sensitive formation of reactive oxygen species in B CLL cells. PEG-catalase prevented the Antho 50-induced reduced cell viability, induction of apoptosis, up-regulation of caspase 3, down-regulation of UHRF1 and Bcl-2, and dephosphorylation of Bad. The present findings indicate that Antho 50 exhibits strong pro-apoptotic activity through redox-sensitive caspase 3 activation-related mechanism in B CLL cells involving dysregulation of Bad/Bcl-2 pathway. This activity is due, at least in part, to a composition rich on glucoside and rutinoside derivatives of delphinidin. They further suggest that Antho 50 has chemotherapeutic potential by targeting selectively B CLL cells.
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
Alhosin, Mahmoud; Université de Strasbourg > Laboratoire de Biophotonique et Pharmacologie
León-González1, Antonio J.; Université de Strasbourg > Laboratoire de Biophotonique et Pharmacologie
Dandache, Israa; Université de Strasbourg > Laboratoire de Biophotonique et Pharmacologie
Lelay, Agnès; Université de Strasbourg > Laboratoire de Biophotonique et Pharmacologie
Rashid, Sherzad K.; Université de Strasbourg > Laboratoire de Biophotonique et Pharmacologie
Kevers, Claire ; Université de Liège - ULiège > Département des sciences de la vie > Département des sciences de la vie
PINCEMAIL, Joël ; Centre Hospitalier Universitaire de Liège - CHU > Chirurgie cardio-vasculaire
Fornecker, Luc-Matthieu; Hôpitaux Universitaires de Strasbourg > Oncologie et Hématologie
Mauvieux, Laurent; Hôpitaux Universitaires de Strasbourg > Oncologie et Hématologie
Herbrecht, Raoul; Hôpitaux Universitaires de Strasbourg > Oncologie et Hématologie
Schini-Kerth, Valérie; Université de Strasbpourg > Laboratoire de Biophotonique et Pharmacologie
Language :
English
Title :
Bilberry extract (Antho 50) selectively induces redox-sensitive caspase 3-related apoptosis in chronic lymphocytic leukemia cells by targeting the Bcl-2/Bad pathway
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