The Mechanism of Action of Biguanides: New Answers to a Complex Question.
biguanides
cancer
complex I
metabolism
metformin
redox
Journal
Cancers
ISSN: 2072-6694
Titre abrégé: Cancers (Basel)
Pays: Switzerland
ID NLM: 101526829
Informations de publication
Date de publication:
30 Jun 2022
30 Jun 2022
Historique:
received:
25
05
2022
revised:
20
06
2022
accepted:
23
06
2022
entrez:
9
7
2022
pubmed:
10
7
2022
medline:
10
7
2022
Statut:
epublish
Résumé
Biguanides are a family of antidiabetic drugs with documented anticancer properties in preclinical and clinical settings. Despite intensive investigation, how they exert their therapeutic effects is still debated. Many studies support the hypothesis that biguanides inhibit mitochondrial complex I, inducing energy stress and activating compensatory responses mediated by energy sensors. However, a major concern related to this "complex" model is that the therapeutic concentrations of biguanides found in the blood and tissues are much lower than the doses required to inhibit complex I, suggesting the involvement of additional mechanisms. This comprehensive review illustrates the current knowledge of pharmacokinetics, receptors, sensors, intracellular alterations, and the mechanism of action of biguanides in diabetes and cancer. The conditions of usage and variables affecting the response to these drugs, the effect on the immune system and microbiota, as well as the results from the most relevant clinical trials in cancer are also discussed.
Identifiants
pubmed: 35804992
pii: cancers14133220
doi: 10.3390/cancers14133220
pmc: PMC9265089
pii:
doi:
Types de publication
Journal Article
Review
Langues
eng
Subventions
Organisme : Italian Association for Cancer Research
ID : IG 2021, code n. 25833
Organisme : Istituto Pasteur
ID : Call 2018 Anna Tramontano
Organisme : Sapienza University of Rome
ID : RG12117A61923A6F
Organisme : Fondazione Umberto Veronesi
ID : Post-Doctoral Fellowship 2022
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