The anti-proliferative activity of D-mannoheptulose against breast cancer cell line through glycolysis inhibition

摘要

Cancer cells are mainly dependent on glycolysis to generate Adenosine Triphosphate (ATP) and intermediates required for cell growth and proliferation. Inhibition of glycolysis might be of therapeutic value in antitumor treatment. We investigated the effects of D-mannoheptulose (MH) as the inhibitor of hexokinase on glycolysis metabolism and apoptosis to prevent the proliferation and inhibit the growth of breast cancer cells (AMJ13 and MCF7) in vitro. Cancer cells were compared with a normal embryo fibroblast (REF) cell line via MTT cytotoxicity assay to determine the IC50 of different MH concentrations (13.125 - 1680 μg/ml) and treated with specific concentrations (250, 125, and 62.5 μg/ml) after incubation for 72h at 37°C. Hexokinase activity, pyruvate, ATP concentration, and acidity were measured in treated and untreated breast cancer and normal cells after treatment with 62.5 μg /ml MH for 72 h at 37°C. Our findings showed that MH inhibited the proliferation of breast cancer cell lines and induced killing by increasing cytotoxicity and apoptosis and decreasing hexokinase activity, pyruvate concentration, ATP, and acidity compared with the normal cell line. In addition, MH had low toxicity against normal cells. In conclusion, our results revealed that MH inhibits the glycolysis pathway by inhibiting hexokinase in breast cancer cells and their proliferation. Therefore, MH can be considered a promising treatment for breast cancer.