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...
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doaj-aa3607fe4ad44687b1bbdf4c123f52382021-08-26T13:34:00ZengMDPI AGBiomolecules2218-273X2021-08-01111231123110.3390/biom11081231Metformin and Cancer Glucose Metabolism: At the Bench or at the Bedside?Cecilia Marini0Vanessa Cossu1Matteo Bauckneht2Francesco Lanfranchi3Stefano Raffa4Anna Maria Orengo5Silvia Ravera6Silvia Bruno7Gianmario Sambuceti8CNR Institute of Molecular Bioimaging and Physiology (IBFM), 20054 Milan, ItalyDepartment of Health Sciences, University of Genoa, 16132 Genoa, ItalyIRCCS Ospedale Policlinico San Martino, 16132 Genoa, ItalyDepartment of Health Sciences, University of Genoa, 16132 Genoa, ItalyDepartment of Health Sciences, University of Genoa, 16132 Genoa, ItalyIRCCS Ospedale Policlinico San Martino, 16132 Genoa, ItalyDepartment of Experimental Medicine, Human Anatomy, University of Genoa, 16132 Genoa, ItalyDepartment of Experimental Medicine, Human Anatomy, University of Genoa, 16132 Genoa, ItalyCNR Institute of Molecular Bioimaging and Physiology (IBFM), 20054 Milan, ItalySeveral 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.https://www.mdpi.com/2218-273X/11/8/1231metforminglucose consumptionFDG PET/CT imagingendoplasmic reticulumtumor metabolismcancer therapy |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Cecilia Marini Vanessa Cossu Matteo Bauckneht Francesco Lanfranchi Stefano Raffa Anna Maria Orengo Silvia Ravera Silvia Bruno Gianmario Sambuceti |
spellingShingle |
Cecilia Marini Vanessa Cossu Matteo Bauckneht Francesco Lanfranchi Stefano Raffa Anna Maria Orengo Silvia Ravera Silvia Bruno Gianmario Sambuceti Metformin and Cancer Glucose Metabolism: At the Bench or at the Bedside? Biomolecules metformin glucose consumption FDG PET/CT imaging endoplasmic reticulum tumor metabolism cancer therapy |
author_facet |
Cecilia Marini Vanessa Cossu Matteo Bauckneht Francesco Lanfranchi Stefano Raffa Anna Maria Orengo Silvia Ravera Silvia Bruno Gianmario Sambuceti |
author_sort |
Cecilia Marini |
title |
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_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_sort |
metformin and cancer glucose metabolism: at the bench or at the bedside? |
publisher |
MDPI AG |
series |
Biomolecules |
issn |
2218-273X |
publishDate |
2021-08-01 |
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. |
topic |
metformin glucose consumption FDG PET/CT imaging endoplasmic reticulum tumor metabolism cancer therapy |
url |
https://www.mdpi.com/2218-273X/11/8/1231 |
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