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Cancers 2019, 11(4), 516; https://doi.org/10.3390/cancers11040516

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

1
School of Pharmacy and Biomedical Sciences, and Curtin Health Innovation Research Institute, Curtin University, Bentley, WA 6102, Australia
2
Centre for Genetic Origins of Health and Disease, Faculty of Health and Medical Science, the University of Western Australia, Perth, WA 6000, Australia
*
Author to whom correspondence should be addressed.
Received: 28 February 2019 / Revised: 16 March 2019 / Accepted: 4 April 2019 / Published: 10 April 2019
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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. View Full-Text
Keywords: HMG-CoA reductase inhibitors; epigenetics; histone acetylation; DNA methylation; HDAC inhibitors; DNMT inhibitors HMG-CoA reductase inhibitors; epigenetics; histone acetylation; DNA methylation; HDAC inhibitors; DNMT inhibitors
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Bridgeman, S.; Northrop, W.; Ellison, G.; Sabapathy, T.; Melton, P.E.; Newsholme, P.; Mamotte, C.D.S. Statins Do Not Directly Inhibit the Activity of Major Epigenetic Modifying Enzymes. Cancers 2019, 11, 516.

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