Sarcosine Up-Regulates Expression of Genes Involved in Cell Cycle Progression of Metastatic Models of Prostate Cancer.
Zbynek HegerMiguel Angel Merlos RodrigoPetr MichalekHana PolanskaMichal MasarikVitezslav VitMariana PlevovaDalibor PacikTomas EckschlagerMarie StiborovaVojtech AdamPublished in: PloS one (2016)
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.
Keyphrases
- cell cycle
- prostate cancer
- induced apoptosis
- squamous cell carcinoma
- small cell lung cancer
- cell proliferation
- cell cycle arrest
- poor prognosis
- healthcare
- radical prostatectomy
- body mass index
- signaling pathway
- oxidative stress
- genome wide
- physical activity
- type diabetes
- electronic health record
- weight loss
- replacement therapy
- pi k akt
- mass spectrometry
- long non coding rna
- binding protein
- social media
- diabetic rats
- lymph node metastasis
- bioinformatics analysis
- body weight
- squamous cell
- high fat diet induced