Bridgeman Stephanie, Northrop Wendy, Ellison Gaewyn, Sabapathy Thiru, Melton Phillip E, Newsholme Philip, Mamotte Cyril D S
School of Pharmacy and Biomedical Sciences, and Curtin Health Innovation Research Institute, Curtin University, Bentley, WA 6102, Australia.
Centre for Genetic Origins of Health and Disease, Faculty of Health and Medical Science, the University of Western Australia, Perth, WA 6000, Australia.
Cancers (Basel). 2019 Apr 10;11(4):516. doi: 10.3390/cancers11040516.
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.
他汀类药物（一类广泛使用的降胆固醇药物）潜在的抗癌作用引发了人们极大的兴趣，诸如HDAC和DNMT抑制剂等表观遗传修饰药物的使用情况亦是如此。我们着手研究他汀类药物对多种细胞系（包括肝癌细胞系、乳腺癌细胞系、白血病巨噬细胞、宫颈腺癌细胞和胰岛素分泌细胞）以及他汀治疗的C57B1/6J小鼠肝脏提取物中表观遗传修饰的影响。细胞或细胞提取物用他汀类药物和既定的表观遗传调节剂进行处理，然后对HDAC、HAT和DNMT活性进行定量分析。我们还通过免疫印迹法检测组蛋白乙酰化情况。他汀类药物既未改变HDAC活性，也未改变HAT活性。因此，他汀治疗后组蛋白H3和H4的乙酰化状态未发生变化。然而，他汀类药物倾向于增加DNMT活性。这些结果表明，如之前在其他地方所报道的那样，直接抑制主要类型的表观遗传修饰酶不太可能是他汀类药物抗癌作用的原因。本研究关注的是对表观遗传酶活性和组蛋白乙酰化的整体影响；他汀类药物是否影响某些基因组区域的表观遗传修饰，尚不能排除，仍有待研究。
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