Abstract
Metformin is a guanidine derivative found in Galega officinalis that is commonly used to treat diabetes mellitus. The mechanism of action of metformin involves regulation of the adenosine monophosphate-activated protein kinase/mammalian target of rapamycin signaling pathway, which is implicated in the control of protein synthesis and cell proliferation. This led to the hypothesis that metformin reduces the risk of cancer and slows tumor growth. Thus, in the present study, the effectiveness of metformin as an antiglioma agent was evaluated using the human T98G glioblastoma multiforme cell line. The viability of the T98G cells was assessed using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Apoptosis was monitored by measuring caspase-3 levels, as well as by terminal deoxynucleotidyl transferase dUTP nick end labeling and staining with acridine orange and ethidium bromide. The results demonstrate that metformin reduced cell viability and caused apoptotic morphological changes in the T98G cells. Furthermore, the caspase-3 levels in the metformin-treated T98G cells were higher than those in the control cells. Metformin induced apoptosis in the T98G cell line in a concentration-dependent manner. Metformin may provide an important contribution to the treatment of glioblastoma multiforme.
Highlights
Metformin is widely used for the treatment of type II diabetes; it promotes lower blood glucose levels by increasing muscle glucose uptake, decreasing insulin resistance and improving insulin sensitivity
These effects of metformin are explained by its activation of the adenosine monophosphate‐activated protein kinase (AMPK)‐liver kinase B1 (LKB1) signaling pathway, downregulation of cyclin D1 and inhibition of mammalian target of rapamycin activity [10,11,12,13]
New approaches have demonstrated that the induction of apoptosis in malignant cells may be a promising strategy in cancer therapy [18]
Summary
Glioblastoma multiforme is the most devastating type of cancer of the central nervous system. Novel approaches are required for glioblastoma treatment, including chemotherapy, radiotherapy, and the targeting of apoptosis and cell survival regulatory machinery [16]. Given the aforementioned characteristics of metformin, it may be a good candidate for the treatment of glioblastoma. Metformin crosses the blood‐brain barrier when administered orally and exerts a direct effect on the central nervous system [17]. In the present study, based on epidemiological, clinical and preclinical investigations, the effect of metformin on the human T98G glioblastoma multiforme cell line was examined. The viability of the T98G cells was assessed using a 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide (MTT) assay. Apoptosis was induced by H2O2 and monitored by measuring caspase‐3 levels, as well as by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) and acridine orange/ethidium bromide staining
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