Inhibition of glycolysis and respiration of sarcoma-180 cells by cyclophosphamide

The malignant cells in tumor are known to exhibit high rate of glycolytic activity leading to high production of lactic acid. The anticancer drug cyclophosphamide has been reported to have a highly promising anticancer activity against fibrosarcoma bearing rats. In the present investigation, the effect of the energy metabolism of sarcoma-180 (S-180) on the mode of action of cyclophosphamide, as well as the effect of cyclophosphamide on the mitochondrial and cellular respiration of S-180 cells was studied. The effects of glucose utilization, pyruvate utilization and lactate formation were studied on whole S-180 cells and S-180 cell-free homogenate. The levels of glycolytic enzymes such as hexokinase and lactate dehydrogenate (LDH) Were estimated. The utilization of glucose and pyruvate was found to decrease which resulted in decreased formation of lactic acid. The mitochondrial respiration was also found to decrease significantly after treatment with cyclophosphamide treated cells. The activity of glycolytic enzymes and mitochondrial respiration were also found to decrease. In conclusion, cyclophosphamide affects both cellular and mitochondrial respiration, leading to reduction of cellular energy pool and thereby resulting in a loss of viability of S-180 cells.