Journal article

Combination treatment of p53-null HL-60 cells with histone deacetylase inhibitors and chlorambucil augments apoptosis and increases BCL6 and p21 gene expression

FAA Kwa, MF Cole-Sinclair, MK Kapuscinski

Current Molecular Pharmacology | BENTHAM SCIENCE PUBL LTD | Published : 2019

Abstract

Background: Treatment of hematological malignancies with conventional DNA-damaging drugs, such as chlorambucil (CLB), commonly results in p53-dependent chemo-resistance. Chromatin modifying agents, such as histone deacetylase inhibitors (HDACIs), sodium butyrate (NaBu) and trichostatin A (TSA), may reverse chemo-resistance by modulating the activity of chromatin remodeling enzymes and/or genes that control cell proliferation, differentiation and survival. Objective: This study examined the potential use of HDACIs and CLB combination therapies in an in vitro chemo-resistant leukemia model. Methods: The p53-null promyelocytic leukemia cell line, HL60, was used as an in vitro model of chemo-res..

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Funding Acknowledgements

The authors wish to acknowledge the generous financial support of the Leukaemia Foundation of Victoria and The University of Melbourne. The funds provided were used to purchase consumables for this study. Dr. Faith Kwa would like to thank The School of Health and Biomedical Sciences of RMIT University for their generous financial contribution to the costs for the publication of figures in colour here. Dr. Miroslav Kapuscinski would like to gratefully acknowledge support from The Centre for Epidemiology and Biostatistics at Melbourne School of Population and Global Health, The University of Melbourne.