Cargando…

Statins Do Not Directly Inhibit the Activity of Major Epigenetic Modifying Enzymes

The potential anticancer effects of statins—a widely used class of cholesterol lowering drugs—has generated significant interest, as has the use of epigenetic modifying drugs such as HDAC and DNMT inhibitors. We set out to investigate the effect of statin drugs on epigenetic modifications in multipl...

Descripción completa

Detalles Bibliográficos
Autores principales: Bridgeman, Stephanie, Northrop, Wendy, Ellison, Gaewyn, Sabapathy, Thiru, Melton, Phillip E., Newsholme, Philip, Mamotte, Cyril D. S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6521159/
https://www.ncbi.nlm.nih.gov/pubmed/30974899
http://dx.doi.org/10.3390/cancers11040516
_version_ 1783418892514754560
author Bridgeman, Stephanie
Northrop, Wendy
Ellison, Gaewyn
Sabapathy, Thiru
Melton, Phillip E.
Newsholme, Philip
Mamotte, Cyril D. S.
author_facet Bridgeman, Stephanie
Northrop, Wendy
Ellison, Gaewyn
Sabapathy, Thiru
Melton, Phillip E.
Newsholme, Philip
Mamotte, Cyril D. S.
author_sort Bridgeman, Stephanie
collection PubMed
description The potential anticancer effects of statins—a widely used class of cholesterol lowering drugs—has generated significant interest, as has the use of epigenetic modifying drugs such as HDAC and DNMT inhibitors. We set out to investigate the effect of statin drugs on epigenetic modifications in multiple cell lines, including hepatocellular carcinoma, breast carcinoma, leukemic macrophages, cervical adenocarcinoma, and insulin-secreting cells, as well as liver extracts from statin-treated C57B1/6J mice. Cells or cell extracts were treated with statins and with established epigenetic modulators, and HDAC, HAT, and DNMT activities were quantified. We also examined histone acetylation by immunoblotting. Statins altered neither HDAC nor HAT activity. Accordingly, acetylation of histones H3 and H4 was unchanged with statin treatment. However, statins tended to increase DNMT activity. These results indicate that direct inhibition of the major classes of epigenetic modifying enzymes, as previously reported elsewhere, is unlikely to contribute to any anticancer effects of statins. This study concerned global effects on epigenetic enzyme activities and histone acetylation; whether statins influence epigenetic modifications in certain genomic regions, cannot be ruled out and remains to be investigated.
format Online
Article
Text
id pubmed-6521159
institution National Center for Biotechnology Information
language English
publishDate 2019
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-65211592019-05-31 Statins Do Not Directly Inhibit the Activity of Major Epigenetic Modifying Enzymes Bridgeman, Stephanie Northrop, Wendy Ellison, Gaewyn Sabapathy, Thiru Melton, Phillip E. Newsholme, Philip Mamotte, Cyril D. S. Cancers (Basel) Article The potential anticancer effects of statins—a widely used class of cholesterol lowering drugs—has generated significant interest, as has the use of epigenetic modifying drugs such as HDAC and DNMT inhibitors. We set out to investigate the effect of statin drugs on epigenetic modifications in multiple cell lines, including hepatocellular carcinoma, breast carcinoma, leukemic macrophages, cervical adenocarcinoma, and insulin-secreting cells, as well as liver extracts from statin-treated C57B1/6J mice. Cells or cell extracts were treated with statins and with established epigenetic modulators, and HDAC, HAT, and DNMT activities were quantified. We also examined histone acetylation by immunoblotting. Statins altered neither HDAC nor HAT activity. Accordingly, acetylation of histones H3 and H4 was unchanged with statin treatment. However, statins tended to increase DNMT activity. These results indicate that direct inhibition of the major classes of epigenetic modifying enzymes, as previously reported elsewhere, is unlikely to contribute to any anticancer effects of statins. This study concerned global effects on epigenetic enzyme activities and histone acetylation; whether statins influence epigenetic modifications in certain genomic regions, cannot be ruled out and remains to be investigated. MDPI 2019-04-10 /pmc/articles/PMC6521159/ /pubmed/30974899 http://dx.doi.org/10.3390/cancers11040516 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Bridgeman, Stephanie
Northrop, Wendy
Ellison, Gaewyn
Sabapathy, Thiru
Melton, Phillip E.
Newsholme, Philip
Mamotte, Cyril D. S.
Statins Do Not Directly Inhibit the Activity of Major Epigenetic Modifying Enzymes
title Statins Do Not Directly Inhibit the Activity of Major Epigenetic Modifying Enzymes
title_full Statins Do Not Directly Inhibit the Activity of Major Epigenetic Modifying Enzymes
title_fullStr Statins Do Not Directly Inhibit the Activity of Major Epigenetic Modifying Enzymes
title_full_unstemmed Statins Do Not Directly Inhibit the Activity of Major Epigenetic Modifying Enzymes
title_short Statins Do Not Directly Inhibit the Activity of Major Epigenetic Modifying Enzymes
title_sort statins do not directly inhibit the activity of major epigenetic modifying enzymes
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6521159/
https://www.ncbi.nlm.nih.gov/pubmed/30974899
http://dx.doi.org/10.3390/cancers11040516
work_keys_str_mv AT bridgemanstephanie statinsdonotdirectlyinhibittheactivityofmajorepigeneticmodifyingenzymes
AT northropwendy statinsdonotdirectlyinhibittheactivityofmajorepigeneticmodifyingenzymes
AT ellisongaewyn statinsdonotdirectlyinhibittheactivityofmajorepigeneticmodifyingenzymes
AT sabapathythiru statinsdonotdirectlyinhibittheactivityofmajorepigeneticmodifyingenzymes
AT meltonphillipe statinsdonotdirectlyinhibittheactivityofmajorepigeneticmodifyingenzymes
AT newsholmephilip statinsdonotdirectlyinhibittheactivityofmajorepigeneticmodifyingenzymes
AT mamottecyrilds statinsdonotdirectlyinhibittheactivityofmajorepigeneticmodifyingenzymes