Investigation into the metabolic effect of sarcosine on prostate cancer
Prostate cancer is one of the most common form of human cancer in the world and the most common form of cancer in men in the Western world. There are many molecular factors of prostate cancer, both proteins and metabolites. A 2009 study by Sreekumar et al found that the N-methyl form of glycine, als...
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| Formato: | H2 |
| Lenguaje: | Inglés sueco |
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SLU/Department of Molecular Sciences
2018
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| Materias: | |
| Acceso en línea: | https://stud.epsilon.slu.se |
| _version_ | 1855572241425629184 |
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| author | Larsson, Simon |
| author_browse | Larsson, Simon |
| author_facet | Larsson, Simon |
| author_sort | Larsson, Simon |
| collection | Epsilon Archive for Student Projects |
| description | Prostate cancer is one of the most common form of human cancer in the world and the most common form of cancer in men in the Western world. There are many molecular factors of prostate cancer, both proteins and metabolites. A 2009 study by Sreekumar et al found that the N-methyl form of glycine, also known as sarcosine, is correlated with more advanced prostate cancer and that it could potentially be driving cancer progression. Since then, a transcriptomic analysis has revealed some of the genes that might be involved in sarcosine-driven prostate cancer progression but the exact mechanism is as of yet not known. We set out to examine the effect of treatment with sarcosine, glycine, N,N-dimethylglycine and alanine on the metabolism of cultured prostate cancer cells and non-malignant immortalized prostate cells. Here we demonstrate that sarcosine changes the metabolism of prostate cancer cells and that broad cellular functions, such as energy metabolism, pyrimidine metabolism and amino acid metabolism are affected. Using NMR metabolomics we showed that the cellular concentrations of glucose, choline, O-phosphocholine, creatine, creatine phosphate, proline and other metabolites are altered as a result of the presence of sarcosine. Previous transcriptomic data has pointed towards the cell cycle as being involved in a potential mechanism of sarcosine-induced prostate cancer progression. Our data suggests significant metabolic involvement as well. Metabolism has seen a resurgence recently in cancer research in general and in this research we demonstrate that is worth exploring deeper in prostate cancer specifically. |
| format | H2 |
| id | RepoSLU13423 |
| institution | Swedish University of Agricultural Sciences |
| language | Inglés swe |
| publishDate | 2018 |
| publishDateSort | 2018 |
| publisher | SLU/Department of Molecular Sciences |
| publisherStr | SLU/Department of Molecular Sciences |
| record_format | eprints |
| spelling | RepoSLU134232018-07-09T08:41:15Z Investigation into the metabolic effect of sarcosine on prostate cancer Larsson, Simon prostate cancer Metabolomics NMR-spectroscopy Metabolism Sarcosine Prostate cancer is one of the most common form of human cancer in the world and the most common form of cancer in men in the Western world. There are many molecular factors of prostate cancer, both proteins and metabolites. A 2009 study by Sreekumar et al found that the N-methyl form of glycine, also known as sarcosine, is correlated with more advanced prostate cancer and that it could potentially be driving cancer progression. Since then, a transcriptomic analysis has revealed some of the genes that might be involved in sarcosine-driven prostate cancer progression but the exact mechanism is as of yet not known. We set out to examine the effect of treatment with sarcosine, glycine, N,N-dimethylglycine and alanine on the metabolism of cultured prostate cancer cells and non-malignant immortalized prostate cells. Here we demonstrate that sarcosine changes the metabolism of prostate cancer cells and that broad cellular functions, such as energy metabolism, pyrimidine metabolism and amino acid metabolism are affected. Using NMR metabolomics we showed that the cellular concentrations of glucose, choline, O-phosphocholine, creatine, creatine phosphate, proline and other metabolites are altered as a result of the presence of sarcosine. Previous transcriptomic data has pointed towards the cell cycle as being involved in a potential mechanism of sarcosine-induced prostate cancer progression. Our data suggests significant metabolic involvement as well. Metabolism has seen a resurgence recently in cancer research in general and in this research we demonstrate that is worth exploring deeper in prostate cancer specifically. Prostatacancer är en av de vanligaste cancertyperna i västvärlden och drabbar runt tiotusen män per år i Sverige. Prostatan är en litet organ som ligger under urinblåsan hos män och vars funktion är att producera och utsöndra viktiga komponenter i sädesvätskan. På grund av den stora mängden lidande och de omfattande ekonomiska kostnader som prostatacancer ligger till grund för i samhället så är behovet av forskning inom området mycket stort. Cancer i prostatan är i sig inte dödligt. När prostatacancer har dödlig utkomst så är det uteslutande i fall där cancern har spridit sig till viktigare organ, så som ben, lungor eller lymfkörtlar. Att cancer sprids kallas metastas och är en komplex biologisk process som består av flera distinkta steg, och som påverkas av många olika faktorer. Tidigare har forskare vid University of Michigan, Ann Arbor visat att metaboliten sarkosin ansamlas i stegvis värre fall av prostatacancer, framför allt då cancern går från att befinna sig lokalt i prostatan till att sprida sig till andra vävnadstyper. I deras artikel beskriver de sarkosin en onkometabolit, det vill säga en metabolit som är kapabel att driva cancers förvärring. Dessutom hävdar de att sarkosin kan användas som analyt i av blod- eller urinprover för att påvisa cancer. Resultaten kring sarkosinets roll inom biomedicinsk analys har ifrågasatts, men resultaten kring dess roll som onkometabolit har inte undersökts i detalj ännu. I experimentet som ligger till grund för den här rapporten har vi tittat närmare på hur närvaron av sarkosin påverkar prostatacellers metabolism. Prover förbereddes genom att inkubera celler i provrör tillsammans med sarkosin eller med någon av tre närbesläktade metaboliter; glycin, dimetylglycin och alanin. Analyserna utfördes med hjälp av en metod som kallas NMR-spektroskopi (Nuclear Magnetic Resonance-spektroskopi), vilket är en kraftfull analysmetod som används för att analysera kolföreningar. Våra resultat indikerar att sarkosins påverkan på celler har en omfattande effekt på cellens metabolism. Flera viktiga cellulära funktioner, så som energiomsättning, användning av aminosyror samt fettomsättning påverkas då sarkosin tillsatts. Resultaten som har genererats inom den här studien kan i framtiden ligga till grund för framsteg med klinisk betydelse. Många av de viktigaste etablerade läkemedlen mot cancer angriper cancerns förmåga att ställa om cellens metabolism och det är en måltavla för forskare som avser att hitta nya läkemedel. En ny infallsvinkel på cancermetabolism i en av de kliniskt viktigaste cancertyperna har därför stor betydelse. SLU/Department of Molecular Sciences 2018 H2 eng swe https://stud.epsilon.slu.se https://stud.epsilon.slu.se/13423/ |
| spellingShingle | prostate cancer Metabolomics NMR-spectroscopy Metabolism Sarcosine Larsson, Simon Investigation into the metabolic effect of sarcosine on prostate cancer |
| title | Investigation into the metabolic effect of sarcosine on prostate cancer |
| title_full | Investigation into the metabolic effect of sarcosine on prostate cancer |
| title_fullStr | Investigation into the metabolic effect of sarcosine on prostate cancer |
| title_full_unstemmed | Investigation into the metabolic effect of sarcosine on prostate cancer |
| title_short | Investigation into the metabolic effect of sarcosine on prostate cancer |
| title_sort | investigation into the metabolic effect of sarcosine on prostate cancer |
| topic | prostate cancer Metabolomics NMR-spectroscopy Metabolism Sarcosine |
| url | https://stud.epsilon.slu.se |