Open Access

REVIEW

Metformin and colorectal cancer

GASTÓN AMABLE#, EDUARDO MARTÍNEZ-LEÓN#, MARÍA E. PICCO, OSVALDO REY
Consejo Nacional de Investigaciones Científicas y Técnicas, Universidad de Buenos Aires, Instituto de Inmunología, Genética y Metabolismo, Facultad de Farmacia y Bioquímica, Hospital de Clínicas “José de San Martín”, Ciudad Autónoma de Buenos Aires, CP1120, Argentina
* Corresponding Author:OSVALDO REY. Email:

BIOCELL 2022, 46(1), 51-59. https://doi.org/10.32604/biocell.2022.017565

Received 05 May 2021; Accepted 10 August 2021; Issue published 28 September 2021

Abstract

Colorectal cancer (CRC) is one of the main causes of cancer-related mortality in the developed world despite recent developments in detection and treatment. Several epidemiological studies indicate that metformin, a widely prescribed antidiabetic drug, exerts a protective effect on different cancers including CRC. Furthermore, a recent double-blind placebo-controlled, randomized trial showed that metformin significantly decreased colorectal adenoma recurrence. Studies exploring the mechanism of action of metformin in cells derived from different types of cancers reported many effects including respiratory chain complex 1 inhibition, Akt phosphorylation inhibition, ATP depletion, PKA activation and Wnt signaling inhibition. However, many of these results were obtained employing metformin at concentrations several fold higher than those achieved in target tissues in diabetic patients receiving therapeutic recommended doses of metformin. In contrast, recent studies obtained with metformin at concentrations compatible with those detected in human intestines revealed that metformin elicit responses that target β-catenin, PI3K/Akt, E-cadherin, p120-catenin and focal adhesion kinase which are key molecules and signaling pathways associated to colorectal cancer development. This brief review revisit several know aspects as well as novel ones on the effects of metformin on cancer cells.

Keywords

Metformin; β-Catenin; E-Cadherin; Colorectal cancer; AMPK; PI3K/AKT; FAK

Cite This Article

AMABLE, G., MARTÍNEZ-LEÓN, E., PICCO, M. E., REY, O. (2022). Metformin and colorectal cancer. BIOCELL, 46(1), 51–59.



This work is licensed under a Creative Commons Attribution 4.0 International License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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