Increased Ammonium Toxicity in Response to Exogenous Glutamine in Metastatic Breast Cancer Cells
Year: 2022
Type: article
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 13C5-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.
Source: Metabolites
Language: English
Subfield: Cancer Research
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,094
Funders: American Cancer Society, Purdue University, Purdue University Center for Cancer Research, National Institutes of Health, National Institute on Alcohol Abuse and Alcoholism, National Cancer Institute, National Center for Research Resources, National Center for Advancing Translational Sciences
Awards: G1078897003, G18525055, G2271608853, G2972882861, The influence of alcohol on the metastatic dormancy of breast cancer, G3905499710, G4407206528, G5359048034, Obesity, Metabolism and Breast Cancer Metastasis, G5695227161, G5730221171, Overcoming metastatic resistance to ErbB-targeted therapies, Breaking the Obesity-Cancer Link: New Targets and Strategies, G7311873837, Indiana Clinical and Translational Science Institute (UL1), G8105576897, G8548593052, G9000114576, Impact of hypoxia on lipid metabolism in obesity-driven breast cancer progression, G967334518
OpenAlex ID: W4282923975