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Relation of exposure to amino acids involved in sarcosine metabolic pathway on behavior of non-tumor and malignant prostatic cell lines

Z. Heger, J. Gumulec, N. Cernei, H. Polanska, M. Raudenska, M. Masarik, T. Eckschlager, M. Stiborova, V. Adam, R. Kizek,

. 2016 ; 76 (7) : 679-90. [pub] 20160205

Language English Country United States

Document type Journal Article, Research Support, Non-U.S. Gov't

Persistent link   https://www.medvik.cz/link/bmc16027692

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.

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$a BACKGROUND: Sarcosine (N-methylglycine) was previously delineated as a substantial oncometabolite of prostate cancer (PCa) and its metabolism seems to be significantly involved in PCa development and behavior. METHODS: We focused on investigation whether the exposure of prostate cells (PNT1A, 22Rv1, and PC-3) to sarcosine-related amino acids (glycine, dimethylglycine, and sarcosine) affects their aggressiveness (cell mobility and division rates, using real-time cell based assay). The effect of supplementation on expression of glycine-N-methyltransferase (GNMT) mRNA was examined using qRT-PCR. Finally, post-treatment amino acids patterns were determined with consequent statistical processing using the Ward's method, factorial ANOVA and principal component analysis (P < 0.05). RESULTS: The highest migration induced sarcosine and glycine in metastatic PC-3 cells (a decrease in relative free area about 53% and 73%). The highest cell division was achieved after treatment of 22Rv1 and PC-3 cells with sarcosine (time required for division decreased by 65% or 45%, when compared to untreated cells). qRT-PCR revealed also significant effects on expression of GNMT. Finally, amino acid profiling shown specific amino acid patterns for each cell line. In both, treated and untreated PC-3 cells significantly higher levels of serine, glutamic acid, and aspartate, linked with prostate cancer progression were found. CONCLUSIONS: Sarcosine-related amino acids can exceptionally affect the behavior of benign and malignant prostate cells.
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$a Gumulec, Jaromir $u Central European Institute of Technology, Brno University of Technology, Brno, Czech Republic, European Union. Faculty of Medicine, Department of Physiology, Masaryk University, Brno, Czech Republic, European Union.
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$a Cernei, Natalia $u Department of Chemistry and Biochemistry, Mendel University in Brno, Brno, Czech Republic, European Union. Central European Institute of Technology, Brno University of Technology, Brno, Czech Republic, European Union.
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$a Polanska, Hana $u Central European Institute of Technology, Brno University of Technology, Brno, Czech Republic, European Union. Faculty of Medicine, Department of Physiology, Masaryk University, Brno, Czech Republic, European Union.
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$a Raudenska, Martina $u Central European Institute of Technology, Brno University of Technology, Brno, Czech Republic, European Union. Faculty of Medicine, Department of Physiology, Masaryk University, Brno, Czech Republic, European Union.
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$a Masarik, Michal $u Central European Institute of Technology, Brno University of Technology, Brno, Czech Republic, European Union. Faculty of Medicine, Department of Physiology, Masaryk University, Brno, Czech Republic, European Union.
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$a Eckschlager, Tomas $u 2nd Faculty of Medicine, Department of Paediatric Haematology and Oncology, Charles University and University Hospital Motol, Czech Republic, European Union.
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$a Stiborova, Marie $u Faculty of Science, Department of Biochemistry, Charles University, Czech Republic, European Union.
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$a Adam, Vojtěch $u Department of Chemistry and Biochemistry, Mendel University in Brno, Brno, Czech Republic, European Union. Central European Institute of Technology, Brno University of Technology, Brno, Czech Republic, European Union. $7 xx0064599
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$a Kizek, Rene $u Department of Chemistry and Biochemistry, Mendel University in Brno, Brno, Czech Republic, European Union. Central European Institute of Technology, Brno University of Technology, Brno, Czech Republic, European Union.
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