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

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.

Statins: Epidrugs with effects on endothelial health?

“…Among them, it would be critical to establish whether some progression or priority exists across epigenetic changes. In addition, discrepant result has been reported indicating that statins do not directly inhibit the activity of epigenetic‐modifying enzymes, such as histone acetylase and deacetylase 22 . This suggests that the epigenetic effects of statins in cardiovascular system need to be further validated.…”

“…In addition, discrepant result has been reported indicating that statins do not directly inhibit the activity of epigenetic-modifying enzymes, such as histone acetylase and deacetylase. 22 This suggests that the epigenetic effects of statins in cardiovascular system need to be further validated. Last but not least, it remains elusive whether epigenetic mechanisms are involved in statinassociated muscle and liver damage.…”

“…It will be of interest to examine whether ten-eleven translocation (TET) demethylases are involved in statin-mediated pharmacological effects. 22…”

“…Contrariwise, increased DNMT activity may be induced by atorvastatin—at 200 µM—in HepG2 cells. It will be of interest to examine whether ten‐eleven translocation (TET) demethylases are involved in statin‐mediated pharmacological effects 22 …”

Epigenetic Consequences of in Utero Exposure to Rosuvastatin: Alteration of Histone Methylation Patterns in Newborn Rat Brains

“…The identification of the genomic sequences involved in the control of the embryonic development of offspring whose mothers had been treated with RST remains a formidable challenge. Interestingly, statins, in general, did not directly inhibit the activity of the major epigenetic modifying enzymes, such as, “writers” or “readers” [ 62 ]. Since 50% of all pregnancies are unplanned [ 63 ], the possibility exists that a pregnant woman may be taking a statin at least for a while.…”