In vitro evaluation of penta-O-galloyl-β-d-glucose (PGG) on miRNA expression and apoptosis in BCR-ABL+ ALL

Abstract Background and objective Acute lymphoblastic leukemia (ALL) is a malignant proliferation of lymphoid cells and BCR - ABL translocation have been reported to have worse prognosis than patients with other sub-types of ALL.One of the underlying mechanisms leading to poor treatment outcome is the aberrant expression of miRNAs that can modulate the epigenetic and genetic pathways leading to survival of cancer cells. Hence, epigenetic regulators are agents that may play a major role in combating this disease which is associated with poor survival rate. The current study aims at investigating the epigenetic modulator penta-O-galloyl-β- d -glucose (PGG) on BCR - ABL + cell line SUP B 1 and BCR - ABL − cell line Jurkat 6. Methods The cell viability of the SUP B 1 and jurkat 6 cells on treatment with PGG was assessed using Trypan blue staining and FITC-Annexin-V and PI assay was used to determine the apoptotic effect of leukemic cells on treatment. The fold change of the miRNA and mRNA expressions in BCR - ABL cell line were studied using qRT-PCR analysis. By western blotting the protein levels of p53, survivin, caspase 3 and AKT were determined Results In the current study, we demonstrated that PGG had an inhibitory effect on the growth of SUP B 1 and Jurkat cells. However, combination therapy of PGG with histone deacetylase inhibitor (HDACi), Vornistat can restore miRNA 203 more effectively than either, as a single agent. Similar results were observed in expression of p53 and other apoptotic regulatory proteins. Conclusion Hence, the present study shows that combinational therapy with PGG and Vorinostat has emerged as a promising treatment which has the potential to serve as a novel targeted therapeutic strategy by regulating epigenetic mechanisms in the treatment of BCR - ABL +  ALL