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

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posted on 2023-05-20, 18:41 authored by Bridgeman, S, Northrop, W, Ellison, G, Sabapathy, T, Phillip MeltonPhillip Melton, Newsholme, P, Mamotte, CDS
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.

History

Publication title

Cancers

Volume

11

Issue

4

Pagination

1-14

ISSN

2072-6694

Department/School

Menzies Institute for Medical Research

Publisher

MDPI

Place of publication

Switzerland

Rights 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/).

Repository Status

  • Open

Socio-economic Objectives

Human pharmaceutical treatments

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