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

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.

The Links between Parkinson’s Disease and Cancer

“…The anti-cancer property of metformin is not fully examined. However, some reports indicate the induction of autophagy and apoptosis among patients with colon cancer, one of the most common entities in oncology [ 225 ]. Metformin pharmacotherapy is related with cell cycle arrest in the G0–G1 phase [ 226 ].…”

Is Metformin a Treatment Opportunity for Colorectal Cancer?

“…(53) Sena et al also demonstrated that metformin has an antiproliferative effect relevant to changes in the expression of Nuclear factor E2-related factor 2 (NRF-2)/NF-κB pathways, additionally an apoptotic effect on human colon cancer cells. (54) Numerous studies have indicated that the antitumour effect of metformin may be due to a relationship between metformin and immune cells. In another study metformin inhibited IL-6-induced epithelial-mesenchymal transition signalling by inhibiting STAT3 phosphorylation in colon cancer lines.…”

Pleiotropic Effects of Metformin on Cancer

“…In the colon carcinoma cell line HT29, MTF induced both autophagy and apoptosis. On the molecular level, MTF increased, in a time- and dose-dependent manner, protein expression of apoptotic peptidase activating factor 1 (APAF1), cleaved poly (ADP-ribose) polymerase 1 (PARP1), autophagosomal marker microtubule associated protein 1 light chain 3 (MAPLC3), and CASP3 while decreasing expression of nuclear factor, erythroid 2 like 2 (NFE2L2; alias, NRF2) and nuclear factor-kappa B (NFKB) [ 82 ].…”