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Statins do not directly inhibit the activity of major epigenetic modifying enzymes

Citation

Bridgeman, S and Northrop, W and Ellison, G and Sabapathy, T and Melton, PE and Newsholme, P and Mamotte, CDS, Statins do not directly inhibit the activity of major epigenetic modifying enzymes, Cancers, 11, (4) pp. 1-14. ISSN 2072-6694 (2019) [Refereed Article]


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Copyright Statement

Copyright 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/).

DOI: doi:10.3390/cancers11040516

Abstract

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.

Item Details

Item Type:Refereed Article
Keywords:DNA methylation D,NMT inhibitors, HDAC inhibitors, HMG-CoA reductase inhibitors, epigenetics, histone acetylation
Research Division:Biological Sciences
Research Group:Genetics
Research Field:Epigenetics (incl. genome methylation and epigenomics)
Objective Division:Manufacturing
Objective Group:Human pharmaceutical products
Objective Field:Human pharmaceutical treatments
UTAS Author:Melton, PE (Dr Phillip Melton)
ID Code:141387
Year Published:2019
Web of Science® Times Cited:2
Deposited By:Menzies Institute for Medical Research
Deposited On:2020-10-16
Last Modified:2021-04-09
Downloads:1 View Download Statistics

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