For generation of energy, cancer cells utilize glycolysis more vigorously than oxidative phosphorylation in mitochondria (Warburg effect). We examined the energy metabolism of four leukemia cell lines by using glycolysis inhibitor, 2-deoxy-d-glucose (2-DG) and inhibitor of oxidative phosphorylation, oligomycin. NB4 was relatively sensitive to 2-DG (IC(50): 5.75 mM), consumed more glucose and produced more lactate (waste product of glycolysis) than the three other cell lines. Consequently, NB4 was considered as a "glycolytic" leukemia cell line. Dependency on glycolysis in NB4 was confirmed by the fact that glucose (+) FCS (-) medium showed more growth and survival than glucose (-) FCS (+) medium. Alternatively, THP-1, most resistant to 2-DG (IC(50): 16.14 mM), was most sensitive to oligomycin. Thus, THP-1 was recognized to be dependent on oxidative phosphorylation. In THP-1, glucose (-) FCS (+) medium showed more growth and survival than glucose (+) FCS (-) medium. The dependency of THP-1 on FCS was explained, at least partly, by fatty acid oxidation because inhibitor of fatty acid β-oxidation, etomoxir, augmented the growth suppression of THP-1 by 2-DG. We also examined the mechanisms by which THP-1 was resistant to, and NB4 was sensitive to 2-DG treatment. In THP-1, AMP kinase (AMPK), which is activated when ATP becomes limiting, was rapidly phosphorylated by 2-DG, and expression of Bcl-2 was augmented, which might result in resistance to 2-DG. On the other hand, AMPK phosphorylation and augmentation of Bcl-2 expression by 2-DG were not observed in NB4, which is 2-DG sensitive. These results will facilitate the future leukemia therapy targeting metabolic pathways.

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These results suggest that the present strategy is useful to advance the clinical application of PGE(1) as a therapeutic agent for vascular disorders.

To investigate possible health effects of mobile phone use, we conducted a double-blind, cross-over provocation study to confirm whether subjects with mobile phone related symptoms (MPRS) are more susceptible than control subjects to the effect of electromagnetic fields (EMF) emitted from base stations. We sent questionnaires to 5,000 women and obtained 2,472 valid responses from possible candidates; from these, we recruited 11 subjects with MPRS and 43 controls. There were four EMF exposure conditions, each of which lasted 30 min: continuous, intermittent, and sham exposure with and without noise. Subjects were exposed to EMF of 2.14 GHz, 10 V/m (W-CDMA), in a shielded room to simulate whole-body exposure to EMF from base stations, although the exposure strength we used was higher than that commonly received from base stations. We measured several psychological and cognitive parameters pre- and post-exposure, and monitored autonomic functions. Subjects were asked to report on their perception of EMF and level of discomfort during the experiment. The MPRS group did not differ from the controls in their ability to detect exposure to EMF; nevertheless they consistently experienced more discomfort, regardless of whether or not they were actually exposed to EMF, and despite the lack of significant changes in their autonomic functions. Thus, the two groups did not differ in their responses to real or sham EMF exposure according to any psychological, cognitive or autonomic assessment. In conclusion, we found no evidence of any causal link between hypersensitivity symptoms and exposure to EMF from base stations.

Some cancer cells depend on glutamine despite of pronounced glycolysis. We examined the glutamine metabolism in leukemia cells, and found that HL-60 cells most depended on glutamine in the 4 acute myelogenous leukemia (AML) cell lines examined: growth of HL-60 cells was most suppressed by glutamine deprivation and by inhibition of glutaminolysis, which was rescued by tricarboxylic acid (TCA) cycle intermediate, oxaloacetic acid. Glutamine is also involved in antioxidant defense function by increasing glutathione. Glutamine deprivation suppressed the glutathione content and elevated reactive oxygen species most evidently in HL-60 cells. Glutamine metabolism might be a therapeutic target in some leukemia.