Sarcosine Up-Regulates Expression of Genes Involved in Cell Cycle Progression of Metastatic Models of Prostate Cancer.
The effects of sarcosine on the processes driving prostate cancer (PCa) development remain still unclear. Herein, we show that a supplementation of metastatic PCa cells (androgen independent PC-3 and androgen dependent LNCaP) with sarcosine stimulates cells proliferation in vitro. Similar stimulatory effects were observed also in PCa murine xenografts, in which sarcosine treatment induced a tumor growth and significantly reduced weight of treated mice (p < 0.05). Determination of sarcosine metabolism-related amino acids and enzymes within tumor mass revealed significantly increased glycine, serine and sarcosine concentrations after treatment accompanied with the increased amount of sarcosine dehydrogenase. In both tumor types, dimethylglycine and glycine-N-methyltransferase were affected slightly, only. To identify the effects of sarcosine treatment on the expression of genes involved in any aspect of cancer development, we further investigated expression profiles of excised tumors using cDNA electrochemical microarray followed by validation using the semi-quantitative PCR. We found 25 differentially expressed genes in PC-3, 32 in LNCaP tumors and 18 overlapping genes. Bioinformatical processing revealed strong sarcosine-related induction of genes involved particularly in a cell cycle progression. Our exploratory study demonstrates that sarcosine stimulates PCa metastatic cells irrespectively of androgen dependence. Overall, the obtained data provides valuable information towards understanding the role of sarcosine in PCa progression and adds another piece of puzzle into a picture of sarcosine oncometabolic potential.
Department of Chemistry and Biochemistry, Mendel University in Brno, Zemedelska 1, CZ-613 00, Brno, Czech Republic.|Central European Institute of Technology, Brno University of Technology, Purkynova 123, Brno, CZ-612 00, Czech Republic.
Zbynek
Z
Heger
Department of Chemistry and Biochemistry, Mendel University in Brno, Zemedelska 1, CZ-613 00, Brno, Czech Republic.|Central European Institute of Technology, Brno University of Technology, Purkynova 123, Brno, CZ-612 00, Czech Republic.
Miguel Angel
MA
Merlos Rodrigo
Department of Chemistry and Biochemistry, Mendel University in Brno, Zemedelska 1, CZ-613 00, Brno, Czech Republic.|Central European Institute of Technology, Brno University of Technology, Purkynova 123, Brno, CZ-612 00, Czech Republic.
Petr
P
Michalek
Department of Physiology, Faculty of Medicine, Masaryk University, Kamenice 5, Brno, CZ-625 00, Czech Republic.
Hana
H
Polanska
Central European Institute of Technology, Brno University of Technology, Purkynova 123, Brno, CZ-612 00, Czech Republic.|Department of Physiology, Faculty of Medicine, Masaryk University, Kamenice 5, Brno, CZ-625 00, Czech Republic.
Michal
M
Masarik
Department of Urology, University Hospital Brno, Jihlavska 20, Brno, CZ-625 00, Czech Republic.
Vitezslav
V
Vit
Department of Urology, University Hospital Brno, Jihlavska 20, Brno, CZ-625 00, Czech Republic.
Mariana
M
Plevova
Department of Urology, University Hospital Brno, Jihlavska 20, Brno, CZ-625 00, Czech Republic.
Dalibor
D
Pacik
Department of Paediatric Haematology and Oncology, 2nd Faculty of Medicine, Charles University, and University Hospital Motol, V Uvalu 84, CZ-150 06, Prague 5, Czech Republic.
Tomas
T
Eckschlager
Department of Biochemistry, Faculty of Science, Charles University, Albertov 2030, CZ-128 40, Prague 2, Czech Republic.
Marie
M
Stiborova
Department of Chemistry and Biochemistry, Mendel University in Brno, Zemedelska 1, CZ-613 00, Brno, Czech Republic.|Central European Institute of Technology, Brno University of Technology, Purkynova 123, Brno, CZ-612 00, Czech Republic.
Vojtech
http://orcid.org/0000-0002-8527-286X
V
Adam
D000818:Animals; D002453:Cell Cycle / Q000187:drug effects* / Q000502:physiology; D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects* / Q000502:physiology; D052138:Genes, Neoplasm / Q000502:physiology*; D050938:Glycine N-Methyltransferase / Q000378:metabolism; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D016133:Polymerase Chain Reaction; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000503:physiopathology; D012521:Sarcosine / Q000378:metabolism / Q000494:pharmacology*; D050892:Sarcosine Dehydrogenase / Q000378:metabolism; D059467:Transcriptome; D015854:Up-Regulation
D050892:Sarcosine Dehydrogenase; D050938:Glycine N-Methyltransferase; D012521:Sarcosine