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

Stephanie Bridgeman, Wendy Northrop, Gaewyn Ellison, Thiru Sabapathy, Phillip E Melton, Philip Newsholme, Cyril D S Mamotte

Research output: Contribution to journalArticle

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.

Original languageEnglish
Article number516
JournalCancers
Volume11
Issue number4
DOIs
Publication statusPublished - 10 Apr 2019

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    Bridgeman, S., Northrop, W., Ellison, G., Sabapathy, T., Melton, P. E., Newsholme, P., & Mamotte, C. D. S. (2019). Statins do not directly inhibit the activity of major epigenetic modifying enzymes. Cancers, 11(4), [516]. https://doi.org/10.3390/cancers11040516