Investigating apoptotic and epigenetic effects of mevastatin and 5-aza-2-deoxycytidine in HL-60 cell line

Statins are the most widely prescribed drugs, used for the treatment of hypercholesterolemia and resulting cardiovascular diseases. They inhibit mevalonate synthesis leading to dramatic reductions in both cholesterol and its isoprenoid intermediates: farnesylpyrophosphate and geranylgeranyl pyrophosphate. For this reason, statins affect posttranslational protein isoprenylation. Thus the effects of statins may be much broader than could be expected only from decrease in cholesterol levels. DNA hypermethylation is a common mechanism for tumour suppressor gene inactivation in hematopoietic malignancies. A number of genes playing roles in apoptotic pathways have been identified to be methylated in cancer cells and restoration of these genes? expressions by DNA methyl transferase inhibitors makes cells sensitive to apoptosis. In this study, we aimed to investigate apoptotic and epigenetic effects of Mevastatin alone and in combination with 5?-aza-2-deoxycitidine (DAC) treatments on HL-60 cell line. We showed that treatment with mevastatin alone and DAC followed by Mevastatin resulted in an apoptotic response in a time and dose dependent manner. We also found that the apoptotic effects of DAC increased in the presence of Mevastatin. These results were also confirmed with appropriate changes in the mRNA expression levels of apoptotic and anti-apoptotic genes, in comparison to the control group. Moreover, CASP3 and CASP8 genes were found to be nonmethylated in HL60 cells. Determination of the exact molecular effects of statins and DAC would allow us to identify new molecular targets for the treatment of the leukemia.