Metabolic profiling of attached and detached metformin and 2-deoxy-D-glucose treated breast cancer cells reveals adaptive changes in metabolome of detached cells

Abstract Anchorage-independent growth of cancer cells in vitro is correlated to metastasis formation in vivo. Metformin use is associated with decreased breast cancer incidence and currently evaluated in cancer clinical trials. The combined treatment with metformin and 2-deoxy-D-glucose (2DG) in vit...

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Autores principales:	Jernej Repas, Elmar Zügner, Boris Gole, Maruša Bizjak, Uroš Potočnik, Christoph Magnes, Mojca Pavlin
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/5817470cab6c436590e69e4e065503a1
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spelling	oai:doaj.org-article:5817470cab6c436590e69e4e065503a12021-11-08T10:46:08ZMetabolic profiling of attached and detached metformin and 2-deoxy-D-glucose treated breast cancer cells reveals adaptive changes in metabolome of detached cells10.1038/s41598-021-98642-02045-2322https://doaj.org/article/5817470cab6c436590e69e4e065503a12021-11-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-98642-0https://doaj.org/toc/2045-2322Abstract Anchorage-independent growth of cancer cells in vitro is correlated to metastasis formation in vivo. Metformin use is associated with decreased breast cancer incidence and currently evaluated in cancer clinical trials. The combined treatment with metformin and 2-deoxy-D-glucose (2DG) in vitro induces detachment of viable MDA-MB-231 breast cancer cells that retain their proliferation capacity. This might be important for cell detachment from primary tumors, but the metabolic changes involved are unknown. We performed LC/MS metabolic profiling on separated attached and detached MDA-MB-231 cells treated with metformin and/or 2DG. High 2DG and metformin plus 2DG altered the metabolic profile similarly to metformin, inferring that metabolic changes are necessary but not sufficient while the specific effects of 2DG are crucial for detachment. Detached cells had higher NADPH levels and lower fatty acids and glutamine levels compared to attached cells, supporting the role of AMPK activation and reductive carboxylation in supporting anchorage-independent survival. Surprisingly, the metabolic profile of detached cells was closer to untreated control cells than attached treated cells, suggesting detachment might help cells adapt to energy stress. Metformin treated cells had higher fatty and amino acid levels with lower purine nucleotide levels, which is relevant for understanding the anticancer mechanisms of metformin.Jernej RepasElmar ZügnerBoris GoleMaruša BizjakUroš PotočnikChristoph MagnesMojca PavlinNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-19 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Jernej Repas Elmar Zügner Boris Gole Maruša Bizjak Uroš Potočnik Christoph Magnes Mojca Pavlin Metabolic profiling of attached and detached metformin and 2-deoxy-D-glucose treated breast cancer cells reveals adaptive changes in metabolome of detached cells
description	Abstract Anchorage-independent growth of cancer cells in vitro is correlated to metastasis formation in vivo. Metformin use is associated with decreased breast cancer incidence and currently evaluated in cancer clinical trials. The combined treatment with metformin and 2-deoxy-D-glucose (2DG) in vitro induces detachment of viable MDA-MB-231 breast cancer cells that retain their proliferation capacity. This might be important for cell detachment from primary tumors, but the metabolic changes involved are unknown. We performed LC/MS metabolic profiling on separated attached and detached MDA-MB-231 cells treated with metformin and/or 2DG. High 2DG and metformin plus 2DG altered the metabolic profile similarly to metformin, inferring that metabolic changes are necessary but not sufficient while the specific effects of 2DG are crucial for detachment. Detached cells had higher NADPH levels and lower fatty acids and glutamine levels compared to attached cells, supporting the role of AMPK activation and reductive carboxylation in supporting anchorage-independent survival. Surprisingly, the metabolic profile of detached cells was closer to untreated control cells than attached treated cells, suggesting detachment might help cells adapt to energy stress. Metformin treated cells had higher fatty and amino acid levels with lower purine nucleotide levels, which is relevant for understanding the anticancer mechanisms of metformin.
format	article
author	Jernej Repas Elmar Zügner Boris Gole Maruša Bizjak Uroš Potočnik Christoph Magnes Mojca Pavlin
author_facet	Jernej Repas Elmar Zügner Boris Gole Maruša Bizjak Uroš Potočnik Christoph Magnes Mojca Pavlin
author_sort	Jernej Repas
title	Metabolic profiling of attached and detached metformin and 2-deoxy-D-glucose treated breast cancer cells reveals adaptive changes in metabolome of detached cells
title_short	Metabolic profiling of attached and detached metformin and 2-deoxy-D-glucose treated breast cancer cells reveals adaptive changes in metabolome of detached cells
title_full	Metabolic profiling of attached and detached metformin and 2-deoxy-D-glucose treated breast cancer cells reveals adaptive changes in metabolome of detached cells
title_fullStr	Metabolic profiling of attached and detached metformin and 2-deoxy-D-glucose treated breast cancer cells reveals adaptive changes in metabolome of detached cells
title_full_unstemmed	Metabolic profiling of attached and detached metformin and 2-deoxy-D-glucose treated breast cancer cells reveals adaptive changes in metabolome of detached cells
title_sort	metabolic profiling of attached and detached metformin and 2-deoxy-d-glucose treated breast cancer cells reveals adaptive changes in metabolome of detached cells
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/5817470cab6c436590e69e4e065503a1
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Metabolic profiling of attached and detached metformin and 2-deoxy-D-glucose treated breast cancer cells reveals adaptive changes in metabolome of detached cells

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