Finding the key of antifolate virtue – investigation of effects on the epigenetic level

Introduction: Due to their mode of action antifolates may lead to instability of DNA molecules as well as demethylation of cytosine residues, what could subsequently result in activation of epigenetically silenced genes. Therefore, we investigated the epigenetic effects of the two classical antifolates methotrexate (MTX) and pemetrexed (PMX) in cell lines. Methods: We performed cytotoxicity assays to determine optimum treatment conditions with MTX and PMX. Extensive MTT tests were carried out to analyze the impact of different concentrations of the drugs and various exposure times on the glycolysis rate of a num…