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

  • Sci Rep. 2015 Mar 11;5:8996. doi: 10.1038/srep08996.
Mahmoud Alhosin  1 ,  Antonio J León-González  1 ,  Israa Dandache  1 ,  Agnès Lelay  2 ,  Sherzad K Rashid  1 ,  Claire Kevers  3 ,  Joël Pincemail  4 ,  Luc-Matthieu Fornecker  5 ,  Laurent Mauvieux  6 ,  Raoul Herbrecht  5 ,  Valérie B Schini-Kerth  1
Affiliations
  • 1. CNRS UMR 7213 Laboratoire de Biophotonique et Pharmacologie, Université de Strasbourg, Faculté de Pharmacie, 74, route du Rhin, 67401 Illkirch, France.
  • 2. 1] CNRS UMR 7213 Laboratoire de Biophotonique et Pharmacologie, Université de Strasbourg, Faculté de Pharmacie, 74, route du Rhin, 67401 Illkirch, France [2] Oncologie et Hématologie, Hôpitaux Universitaires de Strasbourg, Avenue Molière, 67100 Strasbourg, France.
  • 3. University of Liège, Plant Molecular Biology and Biotechnology Unit, B22, Sart Tilman, B-4000 Liège, Belgium.
  • 4. Dept. of Cardiovascular Surgery and CREDEC, Pathology Tower B23, Sart Tilman, B-4000 Liège, Belgium.
  • 5. 1] Oncologie et Hématologie, Hôpitaux Universitaires de Strasbourg, Avenue Molière, 67100 Strasbourg, France [2] Université de Strasbourg, Faculté de Médecine, Strasbourg, France.
  • 6. 1] Université de Strasbourg, Faculté de Médecine, Strasbourg, France [2] Laboratoire d'Hématologie, Hôpitaux Universitaires de Strasbourg, Avenue Molière, 67100 Strasbourg, France.
PMID: 25757575 DOI: 10.1038/srep08996
Abstract

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.

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