Metformin treatment response is dependent on glucose growth conditions and metabolic phenotype in colorectal cancer cells

Abstract Cancer cells exhibit altered metabolism, a phenomenon described a century ago by Otto Warburg. However, metabolic drug targeting is considered an underutilized and poorly understood area of cancer therapy. Metformin, a metabolic drug commonly used to treat type 2 diabetes, has been associat...

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Autores principales:	Abdelnour H. Alhourani, Tia R. Tidwell, Ansooya A. Bokil, Gro V. Røsland, Karl Johan Tronstad, Kjetil Søreide, Hanne R. Hagland
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/6d775d6752384370af9c1a1651d89e30
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spelling	oai:doaj.org-article:6d775d6752384370af9c1a1651d89e302021-12-02T15:45:27ZMetformin treatment response is dependent on glucose growth conditions and metabolic phenotype in colorectal cancer cells10.1038/s41598-021-89861-62045-2322https://doaj.org/article/6d775d6752384370af9c1a1651d89e302021-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-89861-6https://doaj.org/toc/2045-2322Abstract Cancer cells exhibit altered metabolism, a phenomenon described a century ago by Otto Warburg. However, metabolic drug targeting is considered an underutilized and poorly understood area of cancer therapy. Metformin, a metabolic drug commonly used to treat type 2 diabetes, has been associated with lower cancer incidence, although studies are inconclusive concerning effectiveness of the drug in treatment or cancer prevention. The aim of this study was to determine how glucose concentration influences cancer cells’ response to metformin, highlighting why metformin studies are inconsistent. We used two colorectal cancer cell lines with different growth rates and clinically achievable metformin concentrations. We found that fast growing SW948 are more glycolytic in terms of metabolism, while the slower growing SW1116 are reliant on mitochondrial respiration. Both cell lines show inhibitory growth after metformin treatment under physiological glucose conditions, but not in high glucose conditions. Furthermore, SW1116 converges with SW948 at a more glycolytic phenotype after metformin treatment. This metabolic shift is supported by changed GLUT1 expression. Thus, cells having different metabolic phenotypes, show a clear differential response to metformin treatment based on glucose concentration. This demonstrates the importance of growth conditions for experiments or clinical studies involving metabolic drugs such as metformin.Abdelnour H. AlhouraniTia R. TidwellAnsooya A. BokilGro V. RøslandKarl Johan TronstadKjetil SøreideHanne R. HaglandNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Abdelnour H. Alhourani Tia R. Tidwell Ansooya A. Bokil Gro V. Røsland Karl Johan Tronstad Kjetil Søreide Hanne R. Hagland Metformin treatment response is dependent on glucose growth conditions and metabolic phenotype in colorectal cancer cells
description	Abstract Cancer cells exhibit altered metabolism, a phenomenon described a century ago by Otto Warburg. However, metabolic drug targeting is considered an underutilized and poorly understood area of cancer therapy. Metformin, a metabolic drug commonly used to treat type 2 diabetes, has been associated with lower cancer incidence, although studies are inconclusive concerning effectiveness of the drug in treatment or cancer prevention. The aim of this study was to determine how glucose concentration influences cancer cells’ response to metformin, highlighting why metformin studies are inconsistent. We used two colorectal cancer cell lines with different growth rates and clinically achievable metformin concentrations. We found that fast growing SW948 are more glycolytic in terms of metabolism, while the slower growing SW1116 are reliant on mitochondrial respiration. Both cell lines show inhibitory growth after metformin treatment under physiological glucose conditions, but not in high glucose conditions. Furthermore, SW1116 converges with SW948 at a more glycolytic phenotype after metformin treatment. This metabolic shift is supported by changed GLUT1 expression. Thus, cells having different metabolic phenotypes, show a clear differential response to metformin treatment based on glucose concentration. This demonstrates the importance of growth conditions for experiments or clinical studies involving metabolic drugs such as metformin.
format	article
author	Abdelnour H. Alhourani Tia R. Tidwell Ansooya A. Bokil Gro V. Røsland Karl Johan Tronstad Kjetil Søreide Hanne R. Hagland
author_facet	Abdelnour H. Alhourani Tia R. Tidwell Ansooya A. Bokil Gro V. Røsland Karl Johan Tronstad Kjetil Søreide Hanne R. Hagland
author_sort	Abdelnour H. Alhourani
title	Metformin treatment response is dependent on glucose growth conditions and metabolic phenotype in colorectal cancer cells
title_short	Metformin treatment response is dependent on glucose growth conditions and metabolic phenotype in colorectal cancer cells
title_full	Metformin treatment response is dependent on glucose growth conditions and metabolic phenotype in colorectal cancer cells
title_fullStr	Metformin treatment response is dependent on glucose growth conditions and metabolic phenotype in colorectal cancer cells
title_full_unstemmed	Metformin treatment response is dependent on glucose growth conditions and metabolic phenotype in colorectal cancer cells
title_sort	metformin treatment response is dependent on glucose growth conditions and metabolic phenotype in colorectal cancer cells
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/6d775d6752384370af9c1a1651d89e30
work_keys_str_mv	AT abdelnourhalhourani metformintreatmentresponseisdependentonglucosegrowthconditionsandmetabolicphenotypeincolorectalcancercells AT tiartidwell metformintreatmentresponseisdependentonglucosegrowthconditionsandmetabolicphenotypeincolorectalcancercells AT ansooyaabokil metformintreatmentresponseisdependentonglucosegrowthconditionsandmetabolicphenotypeincolorectalcancercells AT grovrøsland metformintreatmentresponseisdependentonglucosegrowthconditionsandmetabolicphenotypeincolorectalcancercells AT karljohantronstad metformintreatmentresponseisdependentonglucosegrowthconditionsandmetabolicphenotypeincolorectalcancercells AT kjetilsøreide metformintreatmentresponseisdependentonglucosegrowthconditionsandmetabolicphenotypeincolorectalcancercells AT hannerhagland metformintreatmentresponseisdependentonglucosegrowthconditionsandmetabolicphenotypeincolorectalcancercells
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Metformin treatment response is dependent on glucose growth conditions and metabolic phenotype in colorectal cancer cells

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