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Metformin and Cancer Glucose Metabolism: At the Bench or at the Bedside?
Several studies reported that metformin, the most widely used drug for type 2 diabetes, might affect cancer aggressiveness. The biguanide seems to directly impair cancer energy asset, with the consequent phosphorylation of AMP-activated protein kinase (AMPK) inhibiting cell proliferation and tumor g...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8392176/ https://www.ncbi.nlm.nih.gov/pubmed/34439897 http://dx.doi.org/10.3390/biom11081231 |
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author | Marini, Cecilia Cossu, Vanessa Bauckneht, Matteo Lanfranchi, Francesco Raffa, Stefano Orengo, Anna Maria Ravera, Silvia Bruno, Silvia Sambuceti, Gianmario |
author_facet | Marini, Cecilia Cossu, Vanessa Bauckneht, Matteo Lanfranchi, Francesco Raffa, Stefano Orengo, Anna Maria Ravera, Silvia Bruno, Silvia Sambuceti, Gianmario |
author_sort | Marini, Cecilia |
collection | PubMed |
description | Several studies reported that metformin, the most widely used drug for type 2 diabetes, might affect cancer aggressiveness. The biguanide seems to directly impair cancer energy asset, with the consequent phosphorylation of AMP-activated protein kinase (AMPK) inhibiting cell proliferation and tumor growth. This action is most often attributed to a well-documented blockage of oxidative phosphorylation (OXPHOS) caused by a direct interference of metformin on Complex I function. Nevertheless, several other pleiotropic actions seem to contribute to the anticancer potential of this biguanide. In particular, in vitro and in vivo experimental studies recently documented that metformin selectively inhibits the uptake of 2-[18F]-Fluoro-2-Deoxy-D-Glucose (FDG), via an impaired catalytic function of the enzyme hexose-6P-dehydrogenase (H6PD). H6PD triggers a still largely uncharacterized pentose-phosphate pathway (PPP) within the endoplasmic reticulum (ER) that has been found to play a pivotal role in feeding the NADPH reductive power for both cellular proliferation and antioxidant responses. Regardless of its exploitability in the clinical setting, this metformin action might configure the ER metabolism as a potential target for innovative therapeutic strategies in patients with solid cancers and potentially modifies the current interpretative model of FDG uptake, attributing PET/CT capability to predict cancer aggressiveness to the activation of H6PD catalytic function. |
format | Online Article Text |
id | pubmed-8392176 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-83921762021-08-28 Metformin and Cancer Glucose Metabolism: At the Bench or at the Bedside? Marini, Cecilia Cossu, Vanessa Bauckneht, Matteo Lanfranchi, Francesco Raffa, Stefano Orengo, Anna Maria Ravera, Silvia Bruno, Silvia Sambuceti, Gianmario Biomolecules Review Several studies reported that metformin, the most widely used drug for type 2 diabetes, might affect cancer aggressiveness. The biguanide seems to directly impair cancer energy asset, with the consequent phosphorylation of AMP-activated protein kinase (AMPK) inhibiting cell proliferation and tumor growth. This action is most often attributed to a well-documented blockage of oxidative phosphorylation (OXPHOS) caused by a direct interference of metformin on Complex I function. Nevertheless, several other pleiotropic actions seem to contribute to the anticancer potential of this biguanide. In particular, in vitro and in vivo experimental studies recently documented that metformin selectively inhibits the uptake of 2-[18F]-Fluoro-2-Deoxy-D-Glucose (FDG), via an impaired catalytic function of the enzyme hexose-6P-dehydrogenase (H6PD). H6PD triggers a still largely uncharacterized pentose-phosphate pathway (PPP) within the endoplasmic reticulum (ER) that has been found to play a pivotal role in feeding the NADPH reductive power for both cellular proliferation and antioxidant responses. Regardless of its exploitability in the clinical setting, this metformin action might configure the ER metabolism as a potential target for innovative therapeutic strategies in patients with solid cancers and potentially modifies the current interpretative model of FDG uptake, attributing PET/CT capability to predict cancer aggressiveness to the activation of H6PD catalytic function. MDPI 2021-08-18 /pmc/articles/PMC8392176/ /pubmed/34439897 http://dx.doi.org/10.3390/biom11081231 Text en © 2021 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 | Review Marini, Cecilia Cossu, Vanessa Bauckneht, Matteo Lanfranchi, Francesco Raffa, Stefano Orengo, Anna Maria Ravera, Silvia Bruno, Silvia Sambuceti, Gianmario Metformin and Cancer Glucose Metabolism: At the Bench or at the Bedside? |
title | Metformin and Cancer Glucose Metabolism: At the Bench or at the Bedside? |
title_full | Metformin and Cancer Glucose Metabolism: At the Bench or at the Bedside? |
title_fullStr | Metformin and Cancer Glucose Metabolism: At the Bench or at the Bedside? |
title_full_unstemmed | Metformin and Cancer Glucose Metabolism: At the Bench or at the Bedside? |
title_short | Metformin and Cancer Glucose Metabolism: At the Bench or at the Bedside? |
title_sort | metformin and cancer glucose metabolism: at the bench or at the bedside? |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8392176/ https://www.ncbi.nlm.nih.gov/pubmed/34439897 http://dx.doi.org/10.3390/biom11081231 |
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