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IJMS, Vol. 19, Pages 1478: Metformin Induces Apoptosis and Alters Cellular Responses to Oxidative Stress in Ht29 Colon Cancer Cells: Preliminary Findings

IJMS, Vol. 19, Pages 1478: Metformin Induces Apoptosis and Alters Cellular Responses to Oxidative Stress in Ht29 Colon Cancer Cells: Preliminary Findings

International Journal of Molecular Sciences doi: 10.3390/ijms19051478

Authors: Paola Sena Stefano Mancini Marta Benincasa Francesco Mariani Carla Palumbo Luca Roncucci

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.

Authors:   Sena, Paola ; Mancini, Stefano ; Benincasa, Marta ; Mariani, Francesco ; Palumbo, Carla ; Roncucci, Luca
Journal:   International Journal of Molecular Sciences
Volume:   19
edition:   5
Year:   2018
Pages:   1478
DOI:   10.3390/ijms19051478
Publication date:   16-May-2018
Facts, background information, dossiers
  • metformin
  • cells
  • oxidative stress
  • tumors
  • safety
  • immunofluorescence
  • flow cytometry
  • confocal microscopy
  • colorectal cancer
  • colon cancer
  • cancer
  • autophagy
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