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.
|Data di pubblicazione:||2018|
|Titolo:||Metformin induces apoptosis and alters cellular responses to oxidative stress in Ht29 colon cancer cells: Preliminary findings|
|Autore/i:||Sena, P; Mancini, S; Benincasa, M; Mariani, F; Palumbo, C; Roncucci, L|
|Digital Object Identifier (DOI):||10.3390/ijms19051478|
|Codice identificativo ISI:||WOS:000435297000214|
|Codice identificativo Scopus:||2-s2.0-85047134422|
|Codice identificativo Pubmed:||29772687|
|Citazione:||Metformin induces apoptosis and alters cellular responses to oxidative stress in Ht29 colon cancer cells: Preliminary findings / Sena, P; Mancini, S; Benincasa, M; Mariani, F; Palumbo, C; Roncucci, L. - In: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES. - ISSN 1661-6596. - 19:5(2018), pp. 1478-1494.|
|Tipologia||Articolo su rivista|
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