Sarcosine degradation pathway is involved in the epigenetics of prostate cells

Abstract

It has been shown that sarcosine suplementation stimulates the proliferation of prostate cells and also their invassiveness. In present study we show that enzymes conected with sarcosine conversion to glycine (sarcosine dehydrogenase, pipecolic acid oxidase) are stimulated due to sarcosine treatment. Further, sarcosine treatment increases S-adenosylmethioneine-to-S-adenosylhomocysteine ratio, which indicates a release and utilization of free methyl groups from sarcosine degradation pathway. We identified the highest induction of global methylation in non-malignant PNT1A cells, but global methylation profiles were altered also in malignant (22Rv1) and metastatic (LNCaP) cells. The influence on methylation changes was further verified using hypomethylating agent 5-azacytidine (5-aza). Co-treatment of prostate cells with 5-aza and sarcosine resulted in decrease in cells invassiveness when compared to treatment with sarcosine alone. This correlates with sarcosine-related hypermethylation of genes involved in cells growth and cell cycle.It has been shown that sarcosine suplementation stimulates the proliferation of prostate cells and also their invassiveness. In present study we show that enzymes conected with sarcosine conversion to glycine (sarcosine dehydrogenase, pipecolic acid oxidase) are stimulated due to sarcosine treatment. Further, sarcosine treatment increases S-adenosylmethioneine-to-S-adenosylhomocysteine ratio, which indicates a release and utilization of free methyl groups from sarcosine degradation pathway. We identified the highest induction of global methylation in non-malignant PNT1A cells, but global methylation profiles were altered also in malignant (22Rv1) and metastatic (LNCaP) cells. The influence on methylation changes was further verified using hypomethylating agent 5-azacytidine (5-aza). Co-treatment of prostate cells with 5-aza and sarcosine resulted in decrease in cells invassiveness when compared to treatment with sarcosine alone. This correlates with sarcosine-related hypermethylation of genes involved in cells growth and cell cycle.