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Int. J. Mol. Sci. 2018, 19(5), 1478; https://doi.org/10.3390/ijms19051478

Metformin Induces Apoptosis and Alters Cellular Responses to Oxidative Stress in Ht29 Colon Cancer Cells: Preliminary Findings

1
Department of Biomedical, Metabolic and Neurosciences, Section of Human Morphology, University of Modena and Reggio Emilia, Policlinico, Via Del Pozzo 71, I-41125 Modena, Italy
2
Department of Diagnostic and Clinical Medicine, and Public Health, University of Modena and Reggio Emilia, Policlinico, Via Del Pozzo 71, I-41125 Modena, Italy
*
Author to whom correspondence should be addressed.
Received: 20 March 2018 / Revised: 25 April 2018 / Accepted: 10 May 2018 / Published: 16 May 2018
(This article belongs to the Special Issue Metformin: Mechanism and Application)
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Abstract

Accumulating evidence suggests that metformin, used as an antidiabetic drug, possesses anti-cancer properties. Metformin reduced the incidence and growth of experimental tumors in vivo. In a randomized clinical trial among nondiabetic patients, metformin treatment significantly decreased the number of aberrant crypt foci compared to the untreated group with a follow-up of 1 month. In our study, HT29 cells were treated with graded concentrations of metformin, 10 mM/25 mM/50 mM for 24/48 h. We performed immunofluorescence experiments by means of confocal microscopy and western blot analysis to evaluate a panel of factors involved in apoptotic/autophagic processes and oxidative stress response. Moreover, HT29 cells treated with metformin were analyzed by a flow cytometry assay to detect the cell apoptotic rate. The results demonstrate that metformin exerts growth inhibitory effects on cultured HT29 cells by increasing both apoptosis and autophagy; moreover, it affects the survival of cultured cells inhibiting the transcriptional activation of Nuclear factor E2-related factor 2 (NRF-2) and nuclear factor-kappa B (NF-κB). The effects of metformin on HT29 cells were dose- and time-dependent. These results are very intriguing since metformin is emerging as a multi-faceted drug: It has a good safety profile and is associated with low cost and might be a promising candidate for the prevention or the treatment of colorectal cancer. View Full-Text
Keywords: colorectal cancer cells; metformin; apoptosis; oxidative stress colorectal cancer cells; metformin; apoptosis; oxidative stress
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).
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Sena, P.; Mancini, S.; Benincasa, M.; Mariani, F.; Palumbo, C.; Roncucci, L. Metformin Induces Apoptosis and Alters Cellular Responses to Oxidative Stress in Ht29 Colon Cancer Cells: Preliminary Findings. Int. J. Mol. Sci. 2018, 19, 1478.

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