Background: Epigenetic dysregulation is a common feature of cancer. Promoter demethylation of tumor-promoting genes and global DNA hypomethylation may trigger tumor progression. Epigenetic changes are unstable; thus, research has focused on detecting remedies that target epigenetic regulators. Previous studies have suggested that concordantly targeting hypomethylation and hypermethylation is beneficial for suppressing both the oncogenic and pro-metastatic functions of cancer cells. Therefore, we aimed to investigate the effect of a combination of S-adenosylmethionine (SAM) and the demethylating agent decitabine on prostate cancer cells. Materials and Methods: Prostate cancer cells (PC-3) were treated with SAM, decitabine, or a combination of both. Proliferation, migration, invasion, and methylation assays were also performed. A transcriptome study was conducted to detect different gene clusters between the treatment groups, followed by analyses using the Kyoto Encyclopedia of Genes and Genomes pathway and ingenuity pathway analysis. Finally, to gain information on differential gene expression, promoter methylation studies were performed. Results: Groups treated with decitabine, SAM, or their combination showed reduced proliferative capacity. The decitabine-treated group showed a marginal increase in cell migration and invasion, whereas the SAM-treated and combination treatment groups showed reduced invasion and migration potential. Methylation assays demonstrated the restoration of decitabine-induced demethylation in prostate cancer samples, whereas the transcriptome study revealed the upregulation of different gene clusters between the treatment groups. Methylation studies confirmed that SAM could restore the decitabine-induced demethylation of proto-oncogenes, but it did not induce the re-methylation of tumor-suppressor genes. Conclusions: Combination treatment with SAM and decitabine had an additive effect and did not nullify each other.

Background: The most critical point in the treatment of prostate cancer is the progression towards a hormone-refractory tumour, making research on alternative therapies necessary. This study focused on the methyl donor S-adenosylmethionine (SAM), which is known to act as an antitumourigenic in several cancer cell lines. Though a genome-wide downregulation of proto-oncogenes in prostate cancer cell lines treated with SAM is obvious, the anticancer effects remain elusive. Thus, in this study, the impact of SAM treatment on the cell cycle, apoptosis and cancer-related pathways was investigated. Methods and results: After performing SAM treatment on prostate cancer cell lines (PC-3 and DU145), a cell-cycle arrest during the S-phase, a downregulation of cyclin A protein levels and an upregulation of p21 cell cycle inhibitor were observed. The proapoptotic Bax/Bcl-2 ratio and the caspase-3 activity were elevated; additionally, the apoptosis rate of SAM treated cells increased significantly in a time-dependent manner. Moreover, immunoblots displayed a downregulation of Erk1/2 and STAT3 phosphorylation accompanied by a reduced expression of the STAT3 protein. Conclusion: SAM caused changes in cancer-related pathways, probably leading to the effects on the cell cycle and apoptosis rate. These results provide deeper insights into the anticancer effects of SAM on prostate cancer cells.