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Journal article

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

From

Department of Molecular Biotechnology and Health Sciences, Molecular Imaging Center, University of Torino, Torino, Italy.1

Centro Ricerche Bracco, Bracco Imaging Spa, Colleretto Giacosa (TO), Italy.2

Albeda Research Aps, Gamle Carlsberg Vej 10, Copenhagen, Denmark.3

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.

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.

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.

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.

Language: English
Year: 2015
Pages: 2296-2305
ISSN: 15222594 and 07403194
Types: Journal article
DOI: 10.1002/mrm.25360

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