Metformin and Cancer Hallmarks: Molecular Mechanisms in Thyroid, Prostate and Head and Neck Cancer Models

Metformin is the most used drug for type 2 diabetes (T2DM). Its antitumor activity has been described by clinical studies showing reduced risk of cancer development in T2DM patients, as well as management of T2DM compared with those receiving other glucose-lowering drugs. Metformin has a plethora of...

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Main Authors: Mirian Galliote Morale, Rodrigo Esaki Tamura, Ileana Gabriela Sanchez Rubio
Format: Article
Language:English
Published: MDPI AG 2022-02-01
Series:Biomolecules
Subjects:
Online Access:https://www.mdpi.com/2218-273X/12/3/357
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author Mirian Galliote Morale
Rodrigo Esaki Tamura
Ileana Gabriela Sanchez Rubio
author_facet Mirian Galliote Morale
Rodrigo Esaki Tamura
Ileana Gabriela Sanchez Rubio
author_sort Mirian Galliote Morale
collection DOAJ
description Metformin is the most used drug for type 2 diabetes (T2DM). Its antitumor activity has been described by clinical studies showing reduced risk of cancer development in T2DM patients, as well as management of T2DM compared with those receiving other glucose-lowering drugs. Metformin has a plethora of molecular actions in cancer cells. This review focused on in vitro data on the action mechanisms of metformin on thyroid, prostate and head and neck cancer. AMPK activation regulating specific downstream targets is a constant antineoplastic activity in different types of cancer; however, AMPK-independent mechanisms are also relevant. In vitro evidence makes it clear that depending on the type of tumor, metformin has different actions; its effects may be modulated by different cell conditions (for instance, presence of HPV infection), or it may regulate tissue-specific factors, such as the Na<sup>+</sup>/I<sup>−</sup> symporter (NIS) and androgen receptors. The hallmarks of cancer are a set of functional features acquired by the cell during malignant development. In vitro studies show that metformin regulates almost all the hallmarks of cancer. Interestingly, metformin is one of these therapeutic agents with the potential to synergize with other chemotherapeutic agents, with low cost, low side effects and high positive consequences. Some questions are still challenging: Are metformin in vitro data able to translate from bench to bedside? Does metformin affect drug resistance? Can metformin be used as a generic anticancer drug for all types of tumors? Which are the specific actions of metformin on the peculiarities of each type of cancer? Several clinical trials are in progress or have been concluded for repurposing metformin as an anticancer drug. The continuous efforts in the field and future in vitro studies will be essential to corroborate clinical trials results and to elucidate the raised questions.
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spelling doaj.art-5609cc43f1fc459ead9a79e3e40fa1752023-11-24T00:34:46ZengMDPI AGBiomolecules2218-273X2022-02-0112335710.3390/biom12030357Metformin and Cancer Hallmarks: Molecular Mechanisms in Thyroid, Prostate and Head and Neck Cancer ModelsMirian Galliote Morale0Rodrigo Esaki Tamura1Ileana Gabriela Sanchez Rubio2Department of Biological Sciences, Federal University of São Paulo, Diadema, Rua Pedro de Toledo 669, 11° Andar, São Paulo 04039-032, BrazilDepartment of Biological Sciences, Federal University of São Paulo, Diadema, Rua Pedro de Toledo 669, 11° Andar, São Paulo 04039-032, BrazilDepartment of Biological Sciences, Federal University of São Paulo, Diadema, Rua Pedro de Toledo 669, 11° Andar, São Paulo 04039-032, BrazilMetformin is the most used drug for type 2 diabetes (T2DM). Its antitumor activity has been described by clinical studies showing reduced risk of cancer development in T2DM patients, as well as management of T2DM compared with those receiving other glucose-lowering drugs. Metformin has a plethora of molecular actions in cancer cells. This review focused on in vitro data on the action mechanisms of metformin on thyroid, prostate and head and neck cancer. AMPK activation regulating specific downstream targets is a constant antineoplastic activity in different types of cancer; however, AMPK-independent mechanisms are also relevant. In vitro evidence makes it clear that depending on the type of tumor, metformin has different actions; its effects may be modulated by different cell conditions (for instance, presence of HPV infection), or it may regulate tissue-specific factors, such as the Na<sup>+</sup>/I<sup>−</sup> symporter (NIS) and androgen receptors. The hallmarks of cancer are a set of functional features acquired by the cell during malignant development. In vitro studies show that metformin regulates almost all the hallmarks of cancer. Interestingly, metformin is one of these therapeutic agents with the potential to synergize with other chemotherapeutic agents, with low cost, low side effects and high positive consequences. Some questions are still challenging: Are metformin in vitro data able to translate from bench to bedside? Does metformin affect drug resistance? Can metformin be used as a generic anticancer drug for all types of tumors? Which are the specific actions of metformin on the peculiarities of each type of cancer? Several clinical trials are in progress or have been concluded for repurposing metformin as an anticancer drug. The continuous efforts in the field and future in vitro studies will be essential to corroborate clinical trials results and to elucidate the raised questions.https://www.mdpi.com/2218-273X/12/3/357metformincancerthyroidprostatehead and neckhallmarks
spellingShingle Mirian Galliote Morale
Rodrigo Esaki Tamura
Ileana Gabriela Sanchez Rubio
Metformin and Cancer Hallmarks: Molecular Mechanisms in Thyroid, Prostate and Head and Neck Cancer Models
Biomolecules
metformin
cancer
thyroid
prostate
head and neck
hallmarks
title Metformin and Cancer Hallmarks: Molecular Mechanisms in Thyroid, Prostate and Head and Neck Cancer Models
title_full Metformin and Cancer Hallmarks: Molecular Mechanisms in Thyroid, Prostate and Head and Neck Cancer Models
title_fullStr Metformin and Cancer Hallmarks: Molecular Mechanisms in Thyroid, Prostate and Head and Neck Cancer Models
title_full_unstemmed Metformin and Cancer Hallmarks: Molecular Mechanisms in Thyroid, Prostate and Head and Neck Cancer Models
title_short Metformin and Cancer Hallmarks: Molecular Mechanisms in Thyroid, Prostate and Head and Neck Cancer Models
title_sort metformin and cancer hallmarks molecular mechanisms in thyroid prostate and head and neck cancer models
topic metformin
cancer
thyroid
prostate
head and neck
hallmarks
url https://www.mdpi.com/2218-273X/12/3/357
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AT ileanagabrielasanchezrubio metforminandcancerhallmarksmolecularmechanismsinthyroidprostateandheadandneckcancermodels