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The Effect of Different Glucose Concentrations on the Antiproliferative Activity of Metformin in MCF-7 Breast Cancer Cells

The glucose-lowering drug metformin has been reported to have anticancer properties through unknown mechanisms. Other unknown factors that may influence its anticancer potential include the glycemic status of the patient. Therefore, the objective of this study is to determine the effect of different...

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Autores principales: Nurzhan, Sholpan, Bekezhankyzy, Zhibek, Ding, Hong, Berdigaliyev, Nurken, Sergazy, Shynggys, Gulyayev, Alexander, Shulgau, Zarina, Triggle, Christopher R., Aljofan, Mohamad
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10537756/
https://www.ncbi.nlm.nih.gov/pubmed/37765157
http://dx.doi.org/10.3390/pharmaceutics15092186
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author Nurzhan, Sholpan
Bekezhankyzy, Zhibek
Ding, Hong
Berdigaliyev, Nurken
Sergazy, Shynggys
Gulyayev, Alexander
Shulgau, Zarina
Triggle, Christopher R.
Aljofan, Mohamad
author_facet Nurzhan, Sholpan
Bekezhankyzy, Zhibek
Ding, Hong
Berdigaliyev, Nurken
Sergazy, Shynggys
Gulyayev, Alexander
Shulgau, Zarina
Triggle, Christopher R.
Aljofan, Mohamad
author_sort Nurzhan, Sholpan
collection PubMed
description The glucose-lowering drug metformin has been reported to have anticancer properties through unknown mechanisms. Other unknown factors that may influence its anticancer potential include the glycemic status of the patient. Therefore, the objective of this study is to determine the effect of different glucose environments on the antiproliferative potency and the cellular mechanism of action of metformin. Human breast cancer cells, MCF-7, were incubated in low, normal, elevated, and high glucose environments and treated with metformin. The antiproliferative potential of metformin and its effect on protein expression as well as its ability to induce cellular apoptosis and autophagy under different glucose environments, were determined using different molecular techniques. Metformin significantly inhibited cellular proliferation in a time- and glucose-concentration-dependent manner. In comparison to elevated glucose, low normal glucose alone induced a significant level of autophagy that was further increased in the presence of metformin. While glucose concentration did not appear to have an effect on the antiproliferative potency of metformin, the cellular basis of action was shown to be glucose-dependent. The antiproliferative mechanism of action of metformin in elevated and low normal glucose environments is mTOR-dependent, whereas, in the high glucose environment, the antiproliferative mechanism is independent of mTOR. This is the first study to report that both the antiproliferative potency and the cellular mechanism of action aredependent on the concentration of glucose.
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spelling pubmed-105377562023-09-29 The Effect of Different Glucose Concentrations on the Antiproliferative Activity of Metformin in MCF-7 Breast Cancer Cells Nurzhan, Sholpan Bekezhankyzy, Zhibek Ding, Hong Berdigaliyev, Nurken Sergazy, Shynggys Gulyayev, Alexander Shulgau, Zarina Triggle, Christopher R. Aljofan, Mohamad Pharmaceutics Article The glucose-lowering drug metformin has been reported to have anticancer properties through unknown mechanisms. Other unknown factors that may influence its anticancer potential include the glycemic status of the patient. Therefore, the objective of this study is to determine the effect of different glucose environments on the antiproliferative potency and the cellular mechanism of action of metformin. Human breast cancer cells, MCF-7, were incubated in low, normal, elevated, and high glucose environments and treated with metformin. The antiproliferative potential of metformin and its effect on protein expression as well as its ability to induce cellular apoptosis and autophagy under different glucose environments, were determined using different molecular techniques. Metformin significantly inhibited cellular proliferation in a time- and glucose-concentration-dependent manner. In comparison to elevated glucose, low normal glucose alone induced a significant level of autophagy that was further increased in the presence of metformin. While glucose concentration did not appear to have an effect on the antiproliferative potency of metformin, the cellular basis of action was shown to be glucose-dependent. The antiproliferative mechanism of action of metformin in elevated and low normal glucose environments is mTOR-dependent, whereas, in the high glucose environment, the antiproliferative mechanism is independent of mTOR. This is the first study to report that both the antiproliferative potency and the cellular mechanism of action aredependent on the concentration of glucose. MDPI 2023-08-23 /pmc/articles/PMC10537756/ /pubmed/37765157 http://dx.doi.org/10.3390/pharmaceutics15092186 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Nurzhan, Sholpan
Bekezhankyzy, Zhibek
Ding, Hong
Berdigaliyev, Nurken
Sergazy, Shynggys
Gulyayev, Alexander
Shulgau, Zarina
Triggle, Christopher R.
Aljofan, Mohamad
The Effect of Different Glucose Concentrations on the Antiproliferative Activity of Metformin in MCF-7 Breast Cancer Cells
title The Effect of Different Glucose Concentrations on the Antiproliferative Activity of Metformin in MCF-7 Breast Cancer Cells
title_full The Effect of Different Glucose Concentrations on the Antiproliferative Activity of Metformin in MCF-7 Breast Cancer Cells
title_fullStr The Effect of Different Glucose Concentrations on the Antiproliferative Activity of Metformin in MCF-7 Breast Cancer Cells
title_full_unstemmed The Effect of Different Glucose Concentrations on the Antiproliferative Activity of Metformin in MCF-7 Breast Cancer Cells
title_short The Effect of Different Glucose Concentrations on the Antiproliferative Activity of Metformin in MCF-7 Breast Cancer Cells
title_sort effect of different glucose concentrations on the antiproliferative activity of metformin in mcf-7 breast cancer cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10537756/
https://www.ncbi.nlm.nih.gov/pubmed/37765157
http://dx.doi.org/10.3390/pharmaceutics15092186
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