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Probing treatment response of glutaminolytic prostate cancer cells to natural drugs with hyperpolarized [5‐ 13 C]glutamine
Author(s) -
Canapè Carolina,
Catanzaro Giuseppina,
Terreno Enzo,
Karlsson Magnus,
Lerche Mathilde Hauge,
Jensen Pernille Rose
Publication year - 2015
Publication title -
magnetic resonance in medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.696
H-Index - 225
eISSN - 1522-2594
pISSN - 0740-3194
DOI - 10.1002/mrm.25360
Subject(s) - glutaminolysis , glutamine , du145 , chemistry , glutaminase , cancer cell , prostate cancer , cancer research , metabolism , cancer , biochemistry , medicine , lncap , amino acid
Purpose 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. Conclusion 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. Magn Reson Med, 2014. © 2014 Wiley Periodicals, Inc. Magn Reson Med 73:2296–2305, 2015. © 2014 Wiley Periodicals, Inc.