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    Effect of nitrogen mustard, a vesicant agent, on lymphocyte energy metabolism
    (Walter De Gruyter Gmbh, 2006) Kenar, Levent; Boyunağa, Hakan; Serdar, Muhittin; Karayilanoğlu, Turan; Erbil, M. Kemal
    Background: The vesicant agents sulfur and nitrogen mustards, which contain chloroethyl groups, are potent inhibitors of DNA synthesis and cell growth, likely changing the utilization of anaerobic glycolysis for energy generation. Methods: To investigate the effect of nitrogen mustard on cellular energy metabolism, lymphocytes treated with increasing doses of mechlorethamine (HN2), a nitrogen mustard and an analogue of sulfur mustard, were incubated with radiolabeled glucose. The rates of aerobic and anaerobic glycolysis were then determined. Results: Glycogen consumption was significantly higher in cells treated with HN2 in a dose-dependent manner compared to untreated cells. Similarly, the amount of end-product lactate was increased, but CO2 was reduced in HN2-treated cells. Conclusions: Lymphocytes normally use aerobic glycolysis under aerobic conditions, but energy metabolism predominantly involved anaerobic glycolysis after severe intoxication with mustard agent.
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    The effects of Ara-C, simvastatin and combo therapy on energy metabolism of HL-60 promyolocytic leukemia cell lines
    (Turkish Biochemistry Society, 2013) Boyuna?a, Hakan; Günnur Dikmen, Z.; Kenar, Levent; Saygun, Oral; Keleş, Hatice; Ugur Ural, Ali; Lale, Mustafa
    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 promyolocytic 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 CO2 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 anaerobic 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. © TurkJBiochem.com.