Probing treatment response of glutaminolytic prostate cancer cells to natural drugs with hyperpolarized [5-C-13]glutamine: Glutaminolysis to Measure Drug Response in Cancer Cells

Carolina Canape, Giuseppina Catanzaro, Enzo Terreno, Magnus Karlsson, Mathilde Hauge Lerche, Pernille Rose Jensen

Research output: Contribution to journalJournal articleResearchpeer-review

Abstract

PurposeThe 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-C-13]glutamine is evaluated as a potential biomarker for noninvasive metabolic measurements of drug response in prostate cancer cells.MethodsHyperpolarized [5-C-13]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.ResultsGlutamine 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-C-13]glutamine as a noninvasive probe. A significant decrease in glutamine metabolism occurs upon apoptotic response to treatment with resveratrol and sulforaphane.ConclusionHyperpolarized NMR using [5-C-13]glutamine as a probe permits the noninvasive observation of glutaminolysis in different cell lines and under different treatment conditions. Hyperpolarized [5-C-13]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. Magn Reson Med, 2014. (c) 2014 Wiley Periodicals, Inc. Magn Reson Med 73:2296-2305, 2015. (c) 2014 Wiley Periodicals, Inc.
Original languageEnglish
JournalMagnetic Resonance in Medicine
Volume73
Issue number6
Pages (from-to)2296-2305
ISSN0740-3194
DOIs
Publication statusPublished - 2015
Externally publishedYes

Keywords

  • drug response
  • glutaminolysis
  • prostate cancer Prostatic Neoplasms (MeSH) urologic disease, reproductive system disease/male, neoplastic disease drug therapy
  • Primates Mammalia Vertebrata Chordata Animalia (Animals, Chordates, Humans, Mammals, Primates, Vertebrates) - Hominidae [86215] DU145 cell line cell_line human prostate cancer cells PC3 cell line cell_line human prostate cancer cells
  • [5-carbon-13]glutamine metabolism
  • resveratrol 501-36-0 antineoplastic-drug
  • sulforaphane 4478-93-7 antineoplastic-drug
  • 02508, Cytology - Human
  • 10060, Biochemistry studies - General
  • 12512, Pathology - Therapy
  • 13002, Metabolism - General metabolism and metabolic pathways
  • 15506, Urinary system - Pathology
  • 16504, Reproductive system - Physiology and biochemistry
  • 16506, Reproductive system - Pathology
  • 22002, Pharmacology - General
  • 22005, Pharmacology - Clinical pharmacology
  • 24004, Neoplasms - Pathology, clinical aspects and systemic effects
  • 24008, Neoplasms - Therapeutic agents and therapy
  • Reproduction
  • invasive biochemical assay clinical techniques, diagnostic techniques
  • NMR laboratory techniques, spectrum analysis techniques
  • Biochemistry and Molecular Biophysics
  • Metabolism
  • Pharmacology
  • Reproductive System
  • Tumor Biology
  • 13C NMR
  • DNP
  • hyperpolarization
  • prostate cancer
  • resveratrol
  • sulforaphane
  • treatment

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