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 stimulator...
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| creator | Heger, Zbynek Merlos Rodrigo, Miguel Angel Michalek, Petr Polanska, Hana Masarik, Michal Vit, Vitezslav Plevova, Mariana Pacik, Dalibor Eckschlager, Tomas Stiborova, Marie Adam, Vojtech |
| description | 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. |
| doi_str_mv | 10.1371/journal.pone.0165830 |
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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.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0165830</identifier><identifier>PMID: 27824899</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Amino acids ; Androgens ; Animal models ; Animals ; Apoptosis ; Biochemistry ; Biology and Life Sciences ; Cancer ; Cancer genetics ; Cancer metastasis ; Cancer therapies ; Cell cycle ; Cell Cycle - drug effects ; Cell Cycle - physiology ; Cell Line, Tumor ; Cell proliferation ; Dimethylglycine ; DNA microarrays ; Electrochemistry ; Enzymes ; Gene amplification ; Gene expression ; Gene Expression Regulation, Neoplastic - drug effects ; Gene Expression Regulation, Neoplastic - physiology ; Genes ; Genes, Neoplasm - physiology ; Glycine ; Glycine N-Methyltransferase - metabolism ; Humans ; Kinases ; Male ; Medicine and Health Sciences ; Metabolism ; Metastases ; Methyltransferase ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; N-Methyltransferase ; Neoplasm Transplantation ; Phosphorylation ; Physiology ; Polymerase Chain Reaction ; Prostate cancer ; Prostatic Neoplasms - metabolism ; Prostatic Neoplasms - physiopathology ; Research and Analysis Methods ; Sarcosine ; Sarcosine - metabolism ; Sarcosine - pharmacology ; Sarcosine dehydrogenase ; Sarcosine Dehydrogenase - metabolism ; Serine ; Supplementation ; Supplements ; Transcriptome ; Tumors ; Up-Regulation ; Urology ; Weight reduction ; Xenografts</subject><ispartof>PloS one, 2016-11, Vol.11 (11), p.e0165830-e0165830</ispartof><rights>COPYRIGHT 2016 Public Library of Science</rights><rights>2016 Heger et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2016 Heger et al 2016 Heger et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c725t-de626e3d40e206ff265ff4d1286ecea9bd44447b019b8d3c13ca5976b75a1a7b3</citedby><cites>FETCH-LOGICAL-c725t-de626e3d40e206ff265ff4d1286ecea9bd44447b019b8d3c13ca5976b75a1a7b3</cites><orcidid>0000-0002-8527-286X</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5100880/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5100880/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23847,27903,27904,53769,53771,79346,79347</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27824899$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Kyprianou, Natasha</contributor><creatorcontrib>Heger, Zbynek</creatorcontrib><creatorcontrib>Merlos Rodrigo, Miguel Angel</creatorcontrib><creatorcontrib>Michalek, Petr</creatorcontrib><creatorcontrib>Polanska, Hana</creatorcontrib><creatorcontrib>Masarik, Michal</creatorcontrib><creatorcontrib>Vit, Vitezslav</creatorcontrib><creatorcontrib>Plevova, Mariana</creatorcontrib><creatorcontrib>Pacik, Dalibor</creatorcontrib><creatorcontrib>Eckschlager, Tomas</creatorcontrib><creatorcontrib>Stiborova, Marie</creatorcontrib><creatorcontrib>Adam, Vojtech</creatorcontrib><title>Sarcosine Up-Regulates Expression of Genes Involved in Cell Cycle Progression of Metastatic Models of Prostate Cancer</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>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.</description><subject>Amino acids</subject><subject>Androgens</subject><subject>Animal models</subject><subject>Animals</subject><subject>Apoptosis</subject><subject>Biochemistry</subject><subject>Biology and Life Sciences</subject><subject>Cancer</subject><subject>Cancer genetics</subject><subject>Cancer metastasis</subject><subject>Cancer therapies</subject><subject>Cell cycle</subject><subject>Cell Cycle - drug effects</subject><subject>Cell Cycle - physiology</subject><subject>Cell Line, Tumor</subject><subject>Cell proliferation</subject><subject>Dimethylglycine</subject><subject>DNA microarrays</subject><subject>Electrochemistry</subject><subject>Enzymes</subject><subject>Gene amplification</subject><subject>Gene expression</subject><subject>Gene Expression Regulation, Neoplastic - drug effects</subject><subject>Gene Expression Regulation, Neoplastic - physiology</subject><subject>Genes</subject><subject>Genes, Neoplasm - physiology</subject><subject>Glycine</subject><subject>Glycine N-Methyltransferase - metabolism</subject><subject>Humans</subject><subject>Kinases</subject><subject>Male</subject><subject>Medicine and Health Sciences</subject><subject>Metabolism</subject><subject>Metastases</subject><subject>Methyltransferase</subject><subject>Mice</subject><subject>Mice, Inbred BALB C</subject><subject>Mice, Nude</subject><subject>N-Methyltransferase</subject><subject>Neoplasm Transplantation</subject><subject>Phosphorylation</subject><subject>Physiology</subject><subject>Polymerase Chain Reaction</subject><subject>Prostate cancer</subject><subject>Prostatic Neoplasms - metabolism</subject><subject>Prostatic Neoplasms - physiopathology</subject><subject>Research and Analysis Methods</subject><subject>Sarcosine</subject><subject>Sarcosine - metabolism</subject><subject>Sarcosine - pharmacology</subject><subject>Sarcosine dehydrogenase</subject><subject>Sarcosine Dehydrogenase - metabolism</subject><subject>Serine</subject><subject>Supplementation</subject><subject>Supplements</subject><subject>Transcriptome</subject><subject>Tumors</subject><subject>Up-Regulation</subject><subject>Urology</subject><subject>Weight reduction</subject><subject>Xenografts</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><sourceid>DOA</sourceid><recordid>eNqNk11v0zAUhiMEYqPwDxBEQkJw0eKPxHZukKZqjEqbhjbGreXYJ20q1-7ipNr-PQ7NpgZNAuci0ZvnvD4-PidJ3mI0w5TjL2vfNU7Z2dY7mCHMckHRs-QYF5RMGUH0-cH3UfIqhDVCORWMvUyOCBckE0VxnHTXqtE-1A7Sm-30CpadVS2E9PRu20AItXepr9IzcFFbuJ23OzBp7dI5WJvO77WF9EfjlwfsBbQqtKqtdXrhDdjQi5HpNUjnymloXicvKmUDvBnek-Tm2-nP-ffp-eXZYn5yPtWc5O3UACMMqMkQEMSqirC8qjKDiWCgQRWlyeLiJcJFKQzVmGqVF5yVPFdY8ZJOkvd73631QQ4VCxILygnBWcEjsdgTxqu13Db1RjX30qta_hF8s5SqiWexIAEZk4Hilch1RgEJhahheYFjTiQjJHp9HXbryg0YDa5tlB2Zjv-4eiWXfidzjJAQKBp8Ggwaf9tBaOWmDjpWWjnwXZ93xmjBaFz_RimniPAYMEk-_IU-XYiBWqp41tpVPqaoe1N5kvEICs76bWdPUPExsKl17MSqjvoo4PMoIDIt3LVL1YUgF9dX_89e_hqzHw_YFSjbroK3XRu7MIzBbA_q2IKhgerxPjCS_SA9VEP2gySHQYph7w7v8jHoYXLob6MiGHk</recordid><startdate>20161108</startdate><enddate>20161108</enddate><creator>Heger, Zbynek</creator><creator>Merlos Rodrigo, Miguel Angel</creator><creator>Michalek, Petr</creator><creator>Polanska, Hana</creator><creator>Masarik, Michal</creator><creator>Vit, Vitezslav</creator><creator>Plevova, Mariana</creator><creator>Pacik, Dalibor</creator><creator>Eckschlager, Tomas</creator><creator>Stiborova, Marie</creator><creator>Adam, Vojtech</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope><orcidid>https://orcid.org/0000-0002-8527-286X</orcidid></search><sort><creationdate>20161108</creationdate><title>Sarcosine Up-Regulates Expression of Genes Involved in Cell Cycle Progression of Metastatic Models of Prostate Cancer</title><author>Heger, Zbynek ; Merlos Rodrigo, Miguel Angel ; Michalek, Petr ; Polanska, Hana ; Masarik, Michal ; Vit, Vitezslav ; Plevova, Mariana ; Pacik, Dalibor ; Eckschlager, Tomas ; Stiborova, Marie ; Adam, Vojtech</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c725t-de626e3d40e206ff265ff4d1286ecea9bd44447b019b8d3c13ca5976b75a1a7b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Amino acids</topic><topic>Androgens</topic><topic>Animal models</topic><topic>Animals</topic><topic>Apoptosis</topic><topic>Biochemistry</topic><topic>Biology and Life Sciences</topic><topic>Cancer</topic><topic>Cancer genetics</topic><topic>Cancer metastasis</topic><topic>Cancer therapies</topic><topic>Cell cycle</topic><topic>Cell Cycle - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Heger, Zbynek</au><au>Merlos Rodrigo, Miguel Angel</au><au>Michalek, Petr</au><au>Polanska, Hana</au><au>Masarik, Michal</au><au>Vit, Vitezslav</au><au>Plevova, Mariana</au><au>Pacik, Dalibor</au><au>Eckschlager, Tomas</au><au>Stiborova, Marie</au><au>Adam, Vojtech</au><au>Kyprianou, Natasha</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Sarcosine Up-Regulates Expression of Genes Involved in Cell Cycle Progression of Metastatic Models of Prostate Cancer</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2016-11-08</date><risdate>2016</risdate><volume>11</volume><issue>11</issue><spage>e0165830</spage><epage>e0165830</epage><pages>e0165830-e0165830</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>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.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>27824899</pmid><doi>10.1371/journal.pone.0165830</doi><tpages>e0165830</tpages><orcidid>https://orcid.org/0000-0002-8527-286X</orcidid><oa>free_for_read</oa></addata></record> |
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| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2016-11, Vol.11 (11), p.e0165830-e0165830 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_1837221497 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; Free Full-Text Journals in Chemistry; Public Library of Science (PLoS) |
| subjects | Amino acids Androgens Animal models Animals Apoptosis Biochemistry Biology and Life Sciences Cancer Cancer genetics Cancer metastasis Cancer therapies Cell cycle Cell Cycle - drug effects Cell Cycle - physiology Cell Line, Tumor Cell proliferation Dimethylglycine DNA microarrays Electrochemistry Enzymes Gene amplification Gene expression Gene Expression Regulation, Neoplastic - drug effects Gene Expression Regulation, Neoplastic - physiology Genes Genes, Neoplasm - physiology Glycine Glycine N-Methyltransferase - metabolism Humans Kinases Male Medicine and Health Sciences Metabolism Metastases Methyltransferase Mice Mice, Inbred BALB C Mice, Nude N-Methyltransferase Neoplasm Transplantation Phosphorylation Physiology Polymerase Chain Reaction Prostate cancer Prostatic Neoplasms - metabolism Prostatic Neoplasms - physiopathology Research and Analysis Methods Sarcosine Sarcosine - metabolism Sarcosine - pharmacology Sarcosine dehydrogenase Sarcosine Dehydrogenase - metabolism Serine Supplementation Supplements Transcriptome Tumors Up-Regulation Urology Weight reduction Xenografts |
| title | Sarcosine Up-Regulates Expression of Genes Involved in Cell Cycle Progression of Metastatic Models of Prostate Cancer |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-27T17%3A12%3A19IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Sarcosine%20Up-Regulates%20Expression%20of%20Genes%20Involved%20in%20Cell%20Cycle%20Progression%20of%20Metastatic%20Models%20of%20Prostate%20Cancer&rft.jtitle=PloS%20one&rft.au=Heger,%20Zbynek&rft.date=2016-11-08&rft.volume=11&rft.issue=11&rft.spage=e0165830&rft.epage=e0165830&rft.pages=e0165830-e0165830&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0165830&rft_dat=%3Cgale_plos_%3EA471838763%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1837221497&rft_id=info:pmid/27824899&rft_galeid=A471838763&rft_doaj_id=oai_doaj_org_article_e0dd4ea7f85c43e08a03d6591ff42422&rfr_iscdi=true |