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Background  Aberrant patterns of DNA methylation are abundant in cancer, and epigenetic pathways are increasingly being targeted in cancer drug treatment. Genetic components of the folate-mediated one-carbon metabolism pathway can affect DNA methylation and other vital cell functions, including DNA synthesis, amino acid biosynthesis, and cell growth.    Results  We used a bioinformatics tool, the Transcriptional Pharmacology Workbench, to analyze temporal changes in gene expression among epigenetic regulators of DNA methylation and demethylation, and one-carbon metabolism genes in response to cancer drug treatment. We analyzed gene expression information from the NCI-60 cancer cell line panel after treatment with five antitumor agents, 5-azacytidine, doxorubicin, vorinostat, paclitaxel, and cisplatin. Each antitumor agent elicited concerted changes in gene expression of multiple pathway components across the cell lines. Expression changes of  FOLR2 ,  SMUG1 ,  GART ,  GADD45A ,  MBD1 ,  MTR ,  MTHFD1 , and  CTH  were significantly correlated with chemosensitivity to some of the agents. Among many genes with concerted expression response to individual antitumor agents were genes encoding DNA methyltransferases  DNMT1 ,  DNMT3A , and  DNMT3B , epigenetic and DNA repair factors  MGMT ,  GADD45A , and  MBD1 , and one-carbon metabolism pathway members  MTHFD1 ,  TYMS ,  DHFR ,  MTR ,  MAT2A ,  SLC19A1 ,  ATIC , and  GART .    Conclusions  These transcriptional changes are likely to influence vital cellular functions of DNA methylation and demethylation, cellular growth, DNA biosynthesis, and DNA repair, and some of them may contribute to cytotoxic and apoptotic action of the drugs. This concerted molecular response was observed in a time-dependent manner, which may provide future guidelines for temporal selection of genetic drug targets for combination drug therapy treatment regimens.    Electronic supplementary material  The online version of this article (doi:10.1186/s13148-016-0240-3) contains supplementary material, which is available to authorized users.

clinical epigenetics

Concerted changes in transcriptional regulation of genes involved in DNA methylation, demethylation, and folate-mediated one-carbon metabolism pathways in the NCI-60 cancer cell line panel in response to cancer drug treatment