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

Scientific Reports
Mahmoud AlhosinValérie B Schini-Kerth

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...Continue Reading

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Citations

Jul 25, 2015·Biochemical Pharmacology·Antonio J León-GonzálezValérie B Schini-Kerth
Feb 22, 2017·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Harsimran Sidhu, Neena Capalash
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Feb 6, 2018·Molecular and Clinical Oncology·Seth P ThibadoBrandon T Goodman
Aug 19, 2017·Oxidative Medicine and Cellular Longevity·Gabriele PizzinoAlessandra Bitto
Jan 2, 2019·Cancers·Mariam AbotalebDietrich Büsselberg
Jun 28, 2019·Frontiers in Oncology·Niaz Mahmood, Shafaat A Rabbani
Jun 3, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Coralia CotoraciAnca Hermenean
Sep 27, 2019·Journal of Agricultural and Food Chemistry·Zhixi ChenLonghuo Wu

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Methods Mentioned

BETA
density-gradient centrifugation
flow cytometry
electrophoresis

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