Glucose deprivation using 2-deoxyglucose and acarbose induce metabolic oxidative stress and apoptosis in female mice bearing breast cancer

A characteristic of cancer cells is increased glucose uptake and glycolysis for energy production and hydroperoxide detoxification due to mitochondrial dysfunction. Thus, inhibition of glucose uptake and glycolysis represent smart novel therapy. We used 2-deoxyglucose (2DG) as a glycolysis inhibitor and acarbose (ACA), a specific alpha-glucosidase inhibitor, to decrease glucose uptake. Mice bearing mammary adenocarcinoma tumors were treated by 2DG and/or ACA. Relative tumor volume, tumor growth inhibition rate, relative body weight, glucose concentration, hexokinase-1 protein level by ELISA, pyruvate, and ATP (glycolysis products), reactive oxygen species (ROS), total glutathione T-GSH, apoptosis, and histopathology were measured in treated and untreated groups. Our results showed that combination therapy inhibited tumor volume and increased tumor growth inhibition rate, body weight reduction, decreasing glucose level, HK-1 level, and inhibition of glycolysis products. In addition, combination therapy induced oxidative stress, increase ROS, and decrease T-GSH. Furthermore, immunohistochemistry examination showed the broader area of apoptosis in breast cancer treated by combination agents. In conclusion, our result revealed that the novel combination inhibits glycolysis and glucose uptake and induced oxidative stress and apoptosis. •ACA and 2DG induced glucose deprivation in breast cancer cells by inhibiting Alpha-glucosidase and competing glucose uptake.•ACA and 2DG combined therapy decrease glycolysis products, resulting in glucose deprivation.•Metabolic oxidative stress induction by ACA and 2DG through increased ROS levels and reduced total glutathione.•ACA and 2DG induced glucose deprivation resulting in cleaved caspase-3 high expression in breast cancer tissue.