Anthocyanin-rich bilberry extract induces apoptosis in acute lymphoblastic leukemia cells via redox-sensitive epigenetic modifications

Polycomb group (PcG) proteins are epigenetic regulators that reduce tumor suppressor gene expression and promote cancer cell survival. The aim of the present study was to determine whether a bilberry extract (Antho 50) inhibits the expression of PcG proteins in Jurkat cells and, if so, to determine the underlying mechanism. Apoptotic rates and the formation of reactive oxygen species (ROS) were assessed by flow cytometry, and protein expression by Western blotting. Antho 50 induced apoptosis, augmented ROS formation, increased p73, p21 and cleaved caspase-3 expression levels, and decreased those of p-Akt, survivin, PcG proteins, HDACs, DNMT1 and UHRF1. The antioxidant enzyme PEG-catalase prevented the formation of ROS and apoptosis induced by Antho 50 and also by H2O2. These findings indicate that Antho 50 promotes apoptosis in Jurkat cells, in part, by decreasing the expression levels of PcG proteins, and, hence, the subsequent PcG proteins-dependent pro-survival events via a redox-dependent mechanism.