BET Inhibition Suppresses S100A8 and S100A9 Expression in Acute Myeloid Leukemia Cells and Synergises with Daunorubicin in Causing Cell Death

S100A8 and S100A9 are both members of the S100 family and have been shown to play roles in myeloid differentiation, autophagy, apoptosis, and chemotherapy resistance. In this study we demonstrate that the BET-bromodomain inhibitor JQ1 causes rapid suppression of S100A8 and S100A9 mRNA and protein in...

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Autores principales: Stewart, Helen J. S., Chaudry, Sabah, Crichlow, Asante, Luiling Feilding, Freya, Chevassut, Timothy J. T.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi 2018
Materias:
Research Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6000862/
https://www.ncbi.nlm.nih.gov/pubmed/29955397
http://dx.doi.org/10.1155/2018/5742954
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author Stewart, Helen J. S.
Chaudry, Sabah
Crichlow, Asante
Luiling Feilding, Freya
Chevassut, Timothy J. T.
author_facet Stewart, Helen J. S.
Chaudry, Sabah
Crichlow, Asante
Luiling Feilding, Freya
Chevassut, Timothy J. T.
author_sort Stewart, Helen J. S.
collection PubMed
description S100A8 and S100A9 are both members of the S100 family and have been shown to play roles in myeloid differentiation, autophagy, apoptosis, and chemotherapy resistance. In this study we demonstrate that the BET-bromodomain inhibitor JQ1 causes rapid suppression of S100A8 and S100A9 mRNA and protein in a reversible manner. In addition, we show that JQ1 synergises with daunorubicin in causing AML cell death. Daunorubicin alone causes a dose- and time-dependent increase in S100A8 and S100A9 protein levels in AML cell lines which is overcome by cotreatment with JQ1. This suggests that JQ1 synergises with daunorubicin in causing apoptosis via suppression of S100A8 and S100A9 levels.
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spelling pubmed-60008622018-06-28 BET Inhibition Suppresses S100A8 and S100A9 Expression in Acute Myeloid Leukemia Cells and Synergises with Daunorubicin in Causing Cell Death Stewart, Helen J. S. Chaudry, Sabah Crichlow, Asante Luiling Feilding, Freya Chevassut, Timothy J. T. Bone Marrow Res Research Article S100A8 and S100A9 are both members of the S100 family and have been shown to play roles in myeloid differentiation, autophagy, apoptosis, and chemotherapy resistance. In this study we demonstrate that the BET-bromodomain inhibitor JQ1 causes rapid suppression of S100A8 and S100A9 mRNA and protein in a reversible manner. In addition, we show that JQ1 synergises with daunorubicin in causing AML cell death. Daunorubicin alone causes a dose- and time-dependent increase in S100A8 and S100A9 protein levels in AML cell lines which is overcome by cotreatment with JQ1. This suggests that JQ1 synergises with daunorubicin in causing apoptosis via suppression of S100A8 and S100A9 levels. Hindawi 2018-05-31 /pmc/articles/PMC6000862/ /pubmed/29955397 http://dx.doi.org/10.1155/2018/5742954 Text en Copyright © 2018 Helen J. S. Stewart et al. https://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Stewart, Helen J. S.
Chaudry, Sabah
Crichlow, Asante
Luiling Feilding, Freya
Chevassut, Timothy J. T.
BET Inhibition Suppresses S100A8 and S100A9 Expression in Acute Myeloid Leukemia Cells and Synergises with Daunorubicin in Causing Cell Death
title BET Inhibition Suppresses S100A8 and S100A9 Expression in Acute Myeloid Leukemia Cells and Synergises with Daunorubicin in Causing Cell Death
title_full BET Inhibition Suppresses S100A8 and S100A9 Expression in Acute Myeloid Leukemia Cells and Synergises with Daunorubicin in Causing Cell Death
title_fullStr BET Inhibition Suppresses S100A8 and S100A9 Expression in Acute Myeloid Leukemia Cells and Synergises with Daunorubicin in Causing Cell Death
title_full_unstemmed BET Inhibition Suppresses S100A8 and S100A9 Expression in Acute Myeloid Leukemia Cells and Synergises with Daunorubicin in Causing Cell Death
title_short BET Inhibition Suppresses S100A8 and S100A9 Expression in Acute Myeloid Leukemia Cells and Synergises with Daunorubicin in Causing Cell Death
title_sort bet inhibition suppresses s100a8 and s100a9 expression in acute myeloid leukemia cells and synergises with daunorubicin in causing cell death
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6000862/
https://www.ncbi.nlm.nih.gov/pubmed/29955397
http://dx.doi.org/10.1155/2018/5742954
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