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Publications

Journal Article Review Epublish 17 citations

PubMed: 38785784 DOI: 10.3390/biology13050302

Metformin: From Diabetes to Cancer-Unveiling Molecular Mechanisms and Therapeutic Strategies.

Biology (Basel) 13(5)

Authors: Emilia Amengual-Cladera, Pere Miquel Morla-Barcelo, Andrea MorĂ¡n-Costoya, Jorge Sastre-Serra, Daniel Gabriel Pons, Adamo Valle, Pilar Roca, Mercedes Nadal-Serrano

Affiliations

  • Grupo Metabolismo EnergĂ©tico y NutriciĂ³n, Instituto Universitario de InvestigaciĂ³n en Ciencias de la Salud (IUNICS), Universitat de les Illes Balears, Ctra. de Valldemossa, km 7.5, 07122 Palma, Illes Balears, Spain. Instituto de InvestigaciĂ³n Sanitaria Illes Balears (IdISBa), 07120 Palma, Illes Balears, Spain.
  • Instituto de InvestigaciĂ³n Sanitaria Illes Balears (IdISBa), 07120 Palma, Illes Balears, Spain.
  • Grupo Multidisciplinar de OncologĂ­a Traslacional, Instituto Universitario de InvestigaciĂ³n en Ciencias de la Salud (IUNICS), Universitat de les Illes Balears, Ctra. de Valldemossa, km 7.5, 07122 Palma, Illes Balears, Spain.
  • Centro de InvestigaciĂ³n BiomĂ©dica en Red FisiopatologĂ­a de la Obesidad y NutriciĂ³n (CIBERobn, CB06/03/0043), Instituto de Salud Carlos III, 28029 Madrid, Spain.
  • Grupo Metabolismo EnergĂ©tico y NutriciĂ³n, Instituto Universitario de InvestigaciĂ³n en Ciencias de la Salud (IUNICS), Universitat de les Illes Balears, Ctra. de Valldemossa, km 7.5, 07122 Palma, Illes Balears, Spain.

Abstract

Metformin, a widely used anti-diabetic drug, has garnered attention for its potential in cancer management, particularly in breast and colorectal cancer. It is established that metformin reduces mitochondrial respiration, but its specific molecular targets within mitochondria vary. Proposed mechanisms include inhibiting mitochondrial respiratory chain Complex I and/or Complex IV, and mitochondrial glycerophosphate dehydrogenase, among others. These actions lead to cellular energy deficits, redox state changes, and several molecular changes that reduce hyperglycemia in type 2 diabetic patients. Clinical evidence supports metformin's role in cancer prevention in type 2 diabetes mellitus patients. Moreover, in these patients with breast and colorectal cancer, metformin consumption leads to an improvement in survival outcomes and prognosis. The synergistic effects of metformin with chemotherapy and immunotherapy highlights its potential as an adjunctive therapy for breast and colorectal cancer. However, nuanced findings underscore the need for further research and stratification by molecular subtype, particularly for breast cancer. This comprehensive review integrates metformin-related findings from epidemiological, clinical, and preclinical studies in breast and colorectal cancer. Here, we discuss current research addressed to define metformin's bioavailability and efficacy, exploring novel metformin-based compounds and drug delivery systems, including derivatives targeting mitochondria, combination therapies, and novel nanoformulations, showing enhanced anticancer effects.

MeSH

Mitochondria, Therapeutics, Colorectal Neoplasms, Breast Neoplasms, Research, Diabetes Mellitus, Type 2, Metformin

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