Increased Ammonium Toxicity in Response to Exogenous Glutamine in Metastatic Breast Cancer Cells

Violet A Kiesel; Madeline P Sheeley; Shawn S Donkin; Michael K Wendt; Stephen D Hursting; Dorothy Teegarden

doi:10.3390/metabo12050469

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Increased Ammonium Toxicity in Response to Exogenous Glutamine in Metastatic Breast Cancer Cells

Journal article

Open access

Peer reviewed

Increased Ammonium Toxicity in Response to Exogenous Glutamine in Metastatic Breast Cancer Cells

Violet A Kiesel, Madeline P Sheeley, Shawn S Donkin, Michael K Wendt, Stephen D Hursting and Dorothy Teegarden

Metabolites, Vol.12(5), p.469

05/23/2022

DOI: 10.3390/metabo12050469

PMCID: PMC9145280

PMID: 35629973

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Abstract

Several cancers, including breast cancers, show dependence on glutamine metabolism. The purpose of the present study was to determine the mechanistic basis and impact of differential glutamine metabolism in nonmetastatic and metastatic murine mammary cancer cells. Universally labeled C -glutamine metabolic tracing, qRT-PCR, measures of reductive-oxidative balance, and exogenous ammonium chloride treatment were used to assess glutamine reprogramming. Results show that 4 mM media concentration of glutamine, compared with 2 mM, reduced viability only in metastatic cells, and that this decrease in viability was accompanied by increased incorporation of glutamine-derived carbon into the tricarboxylic acid (TCA) cycle. While increased glutamine metabolism in metastatic cells occurred in tandem with a decrease in the reduced/oxidized glutathione ratio, treatment with the antioxidant molecule N-acetylcysteine did not rescue cell viability. However, the viability of metastatic cells was more sensitive to ammonium chloride treatment compared with nonmetastatic cells, suggesting a role of metabolic reprogramming in averting nitrogen cytotoxicity in nonmetastatic cells. Overall, these results demonstrate the ability of nonmetastatic cancer cells to reprogram glutamine metabolism and that this ability may be lost in metastatic cells.

glutamine metabolism

breast cancer

metastasis

metabolic reprogramming

ammonium toxicity

Details

Title: Subtitle: Increased Ammonium Toxicity in Response to Exogenous Glutamine in Metastatic Breast Cancer Cells
Creators: Violet A Kiesel - Purdue University West Lafayette
Madeline P Sheeley - Purdue University West Lafayette
Shawn S Donkin - Purdue University West Lafayette
Michael K Wendt - Purdue University West Lafayette
Stephen D Hursting - University of North Carolina at Chapel Hill
Dorothy Teegarden - Purdue University West Lafayette
Resource Type: Journal article
Publication Details: Metabolites, Vol.12(5), p.469
DOI: 10.3390/metabo12050469
PMID: 35629973
PMCID: PMC9145280
NLM abbreviation: Metabolites
ISSN: 2218-1989
eISSN: 2218-1989
Grant note: TR000006 / Indiana Clinical and Translation Science Institute R01CA232589, R35CA197627, R01CA207751, R21AA026675 / NIH HHS R01 CA232589 / NCI NIH HHS RSG-CSM130259 / American Cancer Society
Language: English
Date published: 05/23/2022
Academic Unit: Internal Medicine
Record Identifier: 9984459630902771

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