The Effects of Ara-C, Simvastatin and combo therapy on energy metabolism of HL-60 promyolocytic leukemia cell lines

Abstract

1 Biochemistry, 4 Surgery, 5 Internal ABSTRACT Objective: Cancer cells choose their metabolic pathway depending on the oxygen content and substrate concentration of the medium. A wide spectrum of therapeutic agents regulating the energy metabolism of cancer cells are in still in use. Cytosine arabinoside (Ara-C) is a pyrimidine analogue used in the treatment of acute myeloid leukemia (AML) and simvastatin is an inhibitor of HMG-CoA (3-hydroxy-3-methyl-glutaryl-CoA) reductase, which regulates cholesterol biosynthesis. Thus, this study aimed to assess the energy metabolism of HL-60 promyelocytic leukemia cells and healthy white blood cells, additionally to determine the effects of simvastatin and Ara-C, alone or in combination on the energy metabolism of these cells. Materials and Methods: Healthy white blood cells, untreated and treated HL-60 promyo- locytic leukemia cell lines were incubated for 4 hours with radiolabelled glucose. Following incubation, lactate, which is one of the end products of the carbohydrate catabolism, and radiolabelled CO 2 produced by cells were collected and measured by the liquid scintillation device. In addition, glycogen consumption per hour was determined in each group. Results and Conclusion: We found that untreated HL-60 promyolocytic cells use anaero- bic glycolytic pathway whereas healthy white blood cells use aerobic glycolysis for energy gain. It was concluded that combined use of Ara-C and Simvastatin might lead to significant increase in the rate of aerobic glycolysis of HL-60 promyelocytic cells and the metabolism of these leukemia cells become more similar to the metabolism of healthy white blood cells which they originate from.