Polyphenols act synergistically with doxorubicin and etoposide in leukaemia cell lines

MAHBUB, A A, LE MAITRE, Christine, HAYWOOD-SMALL, Sarah, CROSS, N A and JORDAN-MAHY, Nikki (2015). Polyphenols act synergistically with doxorubicin and etoposide in leukaemia cell lines. Cell Death Discovery, 1, p. 15043.

Preview

PDF Le Maitre Polyphenols act synergistically with doxorubicin.pdf - Published Version Creative Commons Attribution. Download (5MB) | Preview

Abstract

The study aimed to assess the effects of polyphenols when used in combination with doxorubicin and etoposide, and to determine whether polyphenols sensitised leukaemia cells, causing inhibition of cell proliferation, cell cycle arrest and induction of apoptosis. This study is based on findings in solid cancer tumours, which have shown that polyphenols can sensitize cells to chemotherapy, and induce apoptosis and/or cell-cycle arrest. This could enable a reduction of chemotherapy dose and off-target effects, whilst maintaining treatment efficacy. Quercetin, apigenin, emodin, rhein and cis-stilbene were investigated alone and in combination with etoposide and doxorubicin in two lymphoid and two myeloid leukaemia cells lines. Measurements were made of ATP levels (using CellTiter-Glo assay) as an indication of total cell number, cell cycle progression (using propidium iodide staining and flow cytometry) and apoptosis (NucView caspase 3 assay and Hoechst 33342/propidium iodide staining). Effects of combination treatments on caspases 3, 8 and 9 activity were determined using Glo luminescent assays, glutathione levels were measured using the GSH-Glo Glutathione Assay and DNA damage determined by anti-γH2AX staining. Doxorubicin and etoposide in combination with polyphenols synergistically reduced ATP levels, induced apoptosis and increased S and/or G2/M phase cell cycle arrest in lymphoid leukaemia cell lines. However, in the myeloid cell lines the effects of the combination treatments varied; doxorubicin had a synergistic or additive effect when combined with quercetin, apigenin, emodin, and cis-stilbene, but had an antagonistic effect when combined with rhein. Combination treatment caused a synergistic downregulation of glutathione levels and increased DNA damage, driving apoptosis via caspase 8 and 9 activation. However, in myeloid cells where antagonistic effects were observed, this was associated with increased glutathione levels and a reduction in DNA damage and apoptosis. This study has demonstrated that doxorubicin and etoposide activity were enhanced by polyphenols in lymphoid leukaemia cells, however, differential responses were seen in myeloid cells with antagonistic responses seen in some combination therapies.

Item Type:	Article
Research Institute, Centre or Group - Does NOT include content added after October 2018:	Biomedical Research Centre
Identification Number:	https://doi.org/10.1038/cddiscovery.2015.43
Page Range:	p. 15043
Depositing User:	Users 3084 not found.
Date Deposited:	11 Jan 2016 10:40
Last Modified:	18 Mar 2021 06:03
URI:	https://shura.shu.ac.uk/id/eprint/11277

Actions (login required)

View Item

Downloads

Publication Metrics