title: Probing treatment response of glutaminolytic prostate cancer cells to natural drugs with hyperpolarized [5-(13) C]glutamine.
abstract: OBJECTIVE
  The correlation between glutamine metabolism and oncogene expression in cancers has led to a renewed interest in the role of glutamine in cancer cell survival. Hyperpolarized [5-(13) C]glutamine is evaluated as a potential biomarker for noninvasive metabolic measurements of drug response in prostate cancer cells.
  
  
  METHODS
  Hyperpolarized [5-(13) C]glutamine is used to measure glutamine metabolism in two prostate cancer cell lines (PC3 and DU145) before and after treatment with the two natural anticancer drugs resveratrol and sulforaphane. An invasive biochemical assay simulating the hyperpolarized experiment is used to independently quantify glutamine metabolism.
  
  
  RESULTS
  Glutamine metabolism is found to be 4 times higher in the more glutaminolytic DU145 cells compared with PC3 cells under proliferating growth conditions by using hyperpolarized [5-(13) C]glutamine as a noninvasive probe. A significant decrease in glutamine metabolism occurs upon apoptotic response to treatment with resveratrol and sulforaphane.
  
  
  CONCLUSIONS
  Hyperpolarized NMR using [5-(13) C]glutamine as a probe permits the noninvasive observation of glutaminolysis in different cell lines and under different treatment conditions. Hyperpolarized [5-(13) C]glutamine metabolism thus is a promising biomarker for the noninvasive detection of tumor response to treatment, as it directly monitors one of the hallmarks in cancer metabolism - glutaminolysis - in living cells.
authors.affiliation: Department of Molecular Biotechnology and Health Sciences, Molecular Imaging Center, University of Torino, Torino, Italy.
authors.forename: Carolina
authors.initials: C
authors.lastname: Canapè
authors.affiliation: Centro Ricerche Bracco, Bracco Imaging Spa, Colleretto Giacosa (TO), Italy.
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Catanzaro
authors.affiliation: Department of Molecular Biotechnology and Health Sciences, Molecular Imaging Center, University of Torino, Torino, Italy.
authors.forename: Enzo
authors.initials: E
authors.lastname: Terreno
authors.affiliation: Albeda Research Aps, Gamle Carlsberg Vej 10, Copenhagen, Denmark.
authors.forename: Magnus
authors.initials: M
authors.lastname: Karlsson
authors.affiliation: Albeda Research Aps, Gamle Carlsberg Vej 10, Copenhagen, Denmark.
authors.forename: Mathilde Hauge
authors.initials: MH
authors.lastname: Lerche
authors.affiliation: Albeda Research Aps, Gamle Carlsberg Vej 10, Copenhagen, Denmark.
authors.forename: Pernille Rose
authors.initials: PR
authors.lastname: Jensen
mesh_terms: D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D014408:Biomarkers, Tumor / Q000378:metabolism; D002247:Carbon Isotopes; D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid; D003287:Contrast Media; D004797:Enzyme-Linked Immunosorbent Assay; D005682:Gadolinium; D005973:Glutamine / Q000378:metabolism*; D006571:Heterocyclic Compounds; D006801:Humans; D066298:In Vitro Techniques; D017879:Isothiocyanates / Q000494:pharmacology*; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D008297:Male; D009942:Organometallic Compounds; D010641:Phenotype; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism*; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology*; D013454:Sulfoxides
chemical_list: D016588:Anticarcinogenic Agents; D000972:Antineoplastic Agents, Phytogenic; D014408:Biomarkers, Tumor; D002247:Carbon Isotopes; D003287:Contrast Media; D006571:Heterocyclic Compounds; D017879:Isothiocyanates; D009942:Organometallic Compounds; D013267:Stilbenes; D013454:Sulfoxides; C062402:gadoteridol; D005973:Glutamine; D005682:Gadolinium; C016766:sulforaphane; D000077185:Resveratrol
keywords: 13C NMR; DNP; hyperpolarization; prostate cancer; resveratrol; sulforaphane; treatment