Zbynek Heger1,2, Jaromir Gumulec2,3, Natalia Cernei1,2, Hana Polanska2,3, Martina Raudenska2,3, Michal Masarik2,3, Tomas Eckschlager4, Marie Stiborova5, Vojtech Adam1,2, Rene Kizek1,2. 1. Department of Chemistry and Biochemistry, Mendel University in Brno, Brno, Czech Republic, European Union. 2. Central European Institute of Technology, Brno University of Technology, Brno, Czech Republic, European Union. 3. Faculty of Medicine, Department of Physiology, Masaryk University, Brno, Czech Republic, European Union. 4. 2nd Faculty of Medicine, Department of Paediatric Haematology and Oncology, Charles University and University Hospital Motol, Czech Republic, European Union. 5. Faculty of Science, Department of Biochemistry, Charles University, Czech Republic, European Union.
Abstract
BACKGROUND: Sarcosine (N-methylglycine) was previously delineated as a substantial oncometabolite of prostate cancer (PCa) and its metabolism seems to be significantly involved in PCa development and behavior. METHODS: We focused on investigation whether the exposure of prostate cells (PNT1A, 22Rv1, and PC-3) to sarcosine-related amino acids (glycine, dimethylglycine, and sarcosine) affects their aggressiveness (cell mobility and division rates, using real-time cell based assay). The effect of supplementation on expression of glycine-N-methyltransferase (GNMT) mRNA was examined using qRT-PCR. Finally, post-treatment amino acids patterns were determined with consequent statistical processing using the Ward's method, factorial ANOVA and principal component analysis (P < 0.05). RESULTS: The highest migration induced sarcosine and glycine in metastatic PC-3 cells (a decrease in relative free area about 53% and 73%). The highest cell division was achieved after treatment of 22Rv1 and PC-3 cells with sarcosine (time required for division decreased by 65% or 45%, when compared to untreated cells). qRT-PCR revealed also significant effects on expression of GNMT. Finally, amino acid profiling shown specific amino acid patterns for each cell line. In both, treated and untreated PC-3 cells significantly higher levels of serine, glutamic acid, and aspartate, linked with prostate cancer progression were found. CONCLUSIONS: Sarcosine-related amino acids can exceptionally affect the behavior of benign and malignant prostate cells.
BACKGROUND:Sarcosine (N-methylglycine) was previously delineated as a substantial oncometabolite of prostate cancer (PCa) and its metabolism seems to be significantly involved in PCa development and behavior. METHODS: We focused on investigation whether the exposure of prostate cells (PNT1A, 22Rv1, and PC-3) to sarcosine-related amino acids (glycine, dimethylglycine, and sarcosine) affects their aggressiveness (cell mobility and division rates, using real-time cell based assay). The effect of supplementation on expression of glycine-N-methyltransferase (GNMT) mRNA was examined using qRT-PCR. Finally, post-treatment amino acids patterns were determined with consequent statistical processing using the Ward's method, factorial ANOVA and principal component analysis (P < 0.05). RESULTS: The highest migration induced sarcosine and glycine in metastatic PC-3 cells (a decrease in relative free area about 53% and 73%). The highest cell division was achieved after treatment of 22Rv1 and PC-3 cells with sarcosine (time required for division decreased by 65% or 45%, when compared to untreated cells). qRT-PCR revealed also significant effects on expression of GNMT. Finally, amino acid profiling shown specific amino acid patterns for each cell line. In both, treated and untreated PC-3 cells significantly higher levels of serine, glutamic acid, and aspartate, linked with prostate cancer progression were found. CONCLUSIONS:Sarcosine-related amino acids can exceptionally affect the behavior of benign and malignant prostate cells.
Authors: Zbynek Heger; Miguel Angel Merlos Rodrigo; Petr Michalek; Hana Polanska; Michal Masarik; Vitezslav Vit; Mariana Plevova; Dalibor Pacik; Tomas Eckschlager; Marie Stiborova; Vojtech Adam Journal: PLoS One Date: 2016-11-08 Impact factor: 3.240