Glioblastoma (GBM) is the most aggressive primary brain tumor with poor prognosis. Here, we studied the effects of phenformin, a mitochondrial complex I inhibitor and more potent chemical analog of the diabetes drug metformin on the inhibition of cell growth and induction of apoptosis of glioma stem cells (GSCs) using both in vitro and in vivo models. Phenformin inhibited the self-renewal of GS...

The effects of phenformin and ethyloestrenol and phenformin and stanozolol on the clinical state, plasma fibrinolytic activity, and fibrinogen-fibrin-related antigen (F.R.-antigen) were compared with placebo in 13 patients with cutaneous vasculitis. Eight patients showed considerable clinical improvement when taking phenformin and an anabolic steroid; an impaired fibrinolytic activity before tr...

The effect of the hypoglycemic biguanide, phenformin, on the binding of insulin to MCF-7 cells, an in vitro line derived from a human breast cancer, has been investigated. Cells incubated for 24 h in the presence of 1.0 micrograms/ml of phenformin bound 62.2 +/- 8.1% (mean +/- SE) more 125I-insulin than did controls. The phenformin effect was dose-dependent over the concentration range of 0.1 m...

Phenformin, a member of the biguanides class of drugs, has been reported to be efficacious in cancer treatment. The focus of the current study was to establish whether there were direct effects of phenformin on the metabolism and bioenergetics of neuroblastoma SH-SY5Y cancer cells. Cell viability was assessed using the alamar blue assay, flow cytometry analysis using propidium iodide and annexi...

1. Circulating concentrations of intermediary metabolites have been measured after administration of 50 mg of phenformin to normal subjects. 2. Phenformin caused a significant increase in blood lactate, alanine and the lactate/pyruvate ratio but did not affect blood glucose or serum insulin concentrations. 3. There was a significant correlation between the increase in blood lactate concentratio...

Activation of AMP-activated protein kinase (AMPK) by exercise and metformin is beneficial for the treatment of type 2 diabetes. We recently found that, in cultured cells, the LKB1 tumor suppressor protein kinase activates AMPK in response to the metformin analog phenformin and the AMP mimetic drug 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside (AICAR). We have also reported that LKB1 ac...

The effect of 50 mg. of sustained release phenformin capsules administered twice daily was compared with a placebo as an aid to weight reduction in obese non-diabetic patients. Phenformin and placebo were administered alternately in two three-month periods.Weight loss on a 1,200-calorie diet was greater in the first three months than in the second three months regardless of treatment. There was...

BACKGROUND The cross-talk between UPR activation and metabolic stress remains largely unclear. RESULTS Phenformin treatment activates the IRE1α and PERK pathways in an AMPK-dependent manner. CONCLUSION AMPK is required for phenformin-mediated IRE1α and PERK activation. SIGNIFICANCE Our findings demonstrate the cross-talk between UPR and metabolic signals. Activation of the unfolded protei...

Normally the kidneys respond to an acid load by increased ammonia production. In six patients with adult-type diabetes this response was reduced by a mean 50% after a therapeutic dose of phenformin. The reduced ability to compensate for acid loads may be one factor leading to metabolic acidosis and lactoacidosis sometimes associated with phenformin therapy.