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Pharmacol Res. 2016 Nov;113(Pt A):675-685. doi: 10.1016/j.phrs.2016.10.006. Epub 2016 Oct 5.

Metformin: An anti-diabetic drug to fight cancer.

Author information

1
Département Innovation Pharmaceutique, Etablissement Pharmaceutique de l'Assistance Publique des Hôpitaux de Paris (APHP), Agence Générale des Equipements et des Produits de Santé (AGEPS), 7 Rue du Fer à Moulin, 75005 Paris, France. Electronic address: mariedaugan1@gmail.com.
2
Département Innovation Pharmaceutique, Etablissement Pharmaceutique de l'Assistance Publique des Hôpitaux de Paris (APHP), Agence Générale des Equipements et des Produits de Santé (AGEPS), 7 Rue du Fer à Moulin, 75005 Paris, France.
3
Département Innovation Pharmaceutique, Etablissement Pharmaceutique de l'Assistance Publique des Hôpitaux de Paris (APHP), Agence Générale des Equipements et des Produits de Santé (AGEPS), 7 Rue du Fer à Moulin, 75005 Paris, France; Chemical, Genetic and Imaging Pharmacology Laboratory, INSERM U1022, CNRS UMR8151, Chimie ParisTech, Faculty of Pharmacy, Paris Descartes University, Sorbone Paris Cité, Paris, France.

Abstract

Since epidemiologic data have highlighted the positive effects of metformin to reduce cancer incidence and mortality, many in vitro and in vivo studies as well as a large number of clinical trials have been conducted in order to study its potential. The many anticancer actions of metformin lead to a cytostatic effect. Two distinct but not exclusive mechanisms can be implicated in these actions. First, by decreasing insulinemia and glycaemia, metformin can block the PI3K/MAPK signalling pathway implicated in cell growth. Second, metformin can directly act on cancer cells by targeting various pathways including tumour metabolism, inflammation, angiogenesis or cancer stem cells, mainly through the activation of the AMPK pathway. Nonetheless, although metformin alone displays chemopreventive properties, it does not seem to be sufficient to treat cancer, raising the need to be combined with other drugs (e.g. chemotherapy or glycolysis inhibitors) in order to synergistically reveal its cytotoxic action. However, in particular conditions such as specific mutations (e.g. LKB, p53 or OCT1) or low glucose availability, metformin alone does have cytotoxic effects. Thus, it is essential to consider the associated biomarkers in order to determine the potential of metformin in different types of cancers.

KEYWORDS:

AMPK pathway; Biomarkers; CSCs; Cancer; Cytotoxic; Metformin

PMID:
27720766
DOI:
10.1016/j.phrs.2016.10.006
[Indexed for MEDLINE]

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