Bilberry extract (Antho 50) selectively induces redox-sensitive caspase 3-related apoptosis in chronic lymphocytic leukemia cells by targeting the Bcl-2/Bad pathway

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...

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Published in:	Scientific reports Vol. 5; no. 1; p. 8996
Main Authors:	Alhosin, Mahmoud, León-González, Antonio J., Dandache, Israa, Lelay, Agnès, Rashid, Sherzad K., Kevers, Claire, Pincemail, Joël, Fornecker, Luc-Matthieu, Mauvieux, Laurent, Herbrecht, Raoul, Schini-Kerth, Valérie B.
Format:	Journal Article Web Resource
Language:	English
Published:	London Nature Publishing Group UK 11-03-2015 Nature Publishing Group
Subjects:	13/2 13/31 631/67/1990/283/1895 692/308/2778 82 82/80 Adult Aged Aged, 80 and over AKT protein Anthocyanins - pharmacology Apoptosis Apoptosis - drug effects Apoptosis Regulatory Proteins - metabolism Bcl protein Bcl-2 protein bcl-Associated Death Protein - metabolism Biochemistry, biophysics & molecular biology Biochimie, biophysique & biologie moléculaire Caspase Caspase 3 - metabolism Caspase-3 Catalase Cell Line, Tumor Chemotherapy Chronic lymphocytic leukemia Dephosphorylation Female Glucosides - pharmacology Humanities and Social Sciences Humans Leukemia Leukemia, Lymphocytic, Chronic, B-Cell - metabolism Leukocytes (mononuclear) Life Sciences Lymphatic leukemia Lymphocytes B Male Middle Aged multidisciplinary Oxidation-Reduction Peripheral blood mononuclear cells Phenolic compounds Phenols Phosphorylation Plant Extracts - pharmacology Polyethylene glycol Proto-Oncogene Proteins c-bcl-2 - metabolism Reactive oxygen species Reactive Oxygen Species - metabolism Science Sciences du vivant Signal Transduction - drug effects Vaccinium myrtillus - chemistry
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Summary:	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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 PMCID: PMC4355738 scopus-id:2-s2.0-84924908487
ISSN:	2045-2322 2045-2322
DOI:	10.1038/srep08996