Bilberry extract (Antho 50) selectively induces redox-sensitive caspase 3-related apoptosis in chronic lymphocytic leukemia cells by targeting the Bcl-2/Bad pathway.
Fiche publication
Date publication
mars 2015
Journal
Scientific reports
Auteurs
Membres identifiés du Cancéropôle Est :
Pr HERBRECHT Raoul, Pr MAUVIEUX Laurent, Pr SCHINI-KERTH Valérie, Pr FORNECKER Luc-Matthieu
Tous les auteurs :
Alhosin M, León-González AJ, Dandache I, Lelay A, Rashid SK, Kevers C, Pincemail J, Fornecker LM, Mauvieux L, Herbrecht R, Schini-Kerth VB
Lien Pubmed
Résumé
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 but little or no effect in PBMCs. Among the main phenolic compounds of the bilberry extract, delphinidin-3-O-glucoside and delphinidin-3-O-rutinoside induced a pro-apoptotic effect. Antho 50-induced apoptosis is associated with activation of caspase 3, down-regulation of UHRF1, a rapid dephosphorylation of Akt and Bad, and down-regulation of Bcl-2. Antho 50 significantly induced PEG-catalase-sensitive formation of reactive oxygen species in B CLL cells. PEG-catalase prevented the Antho 50-induced induction of apoptosis and related signaling. 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 the Bad/Bcl-2 pathway. This activity of Antho 50 involves the glucoside and rutinoside derivatives of delphinidin. They further suggest that Antho 50 has chemotherapeutic potential by targeting selectively B CLL cells.
Mots clés
Adult, Aged, Aged, 80 and over, Anthocyanins, pharmacology, Apoptosis, drug effects, Apoptosis Regulatory Proteins, metabolism, Caspase 3, metabolism, Cell Line, Tumor, Female, Glucosides, pharmacology, Humans, Leukemia, Lymphocytic, Chronic, B-Cell, metabolism, Male, Middle Aged, Oxidation-Reduction, Phosphorylation, Plant Extracts, pharmacology, Proto-Oncogene Proteins c-bcl-2, metabolism, Reactive Oxygen Species, metabolism, Signal Transduction, drug effects, Vaccinium myrtillus, chemistry, bcl-Associated Death Protein, metabolism
Référence
Sci Rep. 2015 Mar;5:8996