Investigation into the metabolic effect of sarcosine on prostate cancer

Sammanfattning: Prostate cancer is one of the most common form of human cancer in the world and the most common form of cancer in men in the Western world. There are many molecular factors of prostate cancer, both proteins and metabolites. A 2009 study by Sreekumar et al found that the N-methyl form of glycine, also known as sarcosine, is correlated with more advanced prostate cancer and that it could potentially be driving cancer progression. Since then, a transcriptomic analysis has revealed some of the genes that might be involved in sarcosine-driven prostate cancer progression but the exact mechanism is as of yet not known. We set out to examine the effect of treatment with sarcosine, glycine, N,N-dimethylglycine and alanine on the metabolism of cultured prostate cancer cells and non-malignant immortalized prostate cells. Here we demonstrate that sarcosine changes the metabolism of prostate cancer cells and that broad cellular functions, such as energy metabolism, pyrimidine metabolism and amino acid metabolism are affected. Using NMR metabolomics we showed that the cellular concentrations of glucose, choline, O-phosphocholine, creatine, creatine phosphate, proline and other metabolites are altered as a result of the presence of sarcosine. Previous transcriptomic data has pointed towards the cell cycle as being involved in a potential mechanism of sarcosine-induced prostate cancer progression. Our data suggests significant metabolic involvement as well. Metabolism has seen a resurgence recently in cancer research in general and in this research we demonstrate that is worth exploring deeper in prostate cancer specifically.