Importance of glutamine metabolism in leukemia cells by energy production through TCA cycle and by redox homeostasis.
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.
Department of Internal Medicine, Division of Hematology, Aichi Medical University School of Medicine , Nagakute, Aichi , Japan.
Mineaki
M
Goto
Hiroshi
H
Miwa
Masato
M
Shikami
Norikazu
N
Tsunekawa-Imai
Kazuto
K
Suganuma
Shohei
S
Mizuno
Miyuki
M
Takahashi
Motonori
M
Mizutani
Ichiro
I
Hanamura
Masakazu
M
Nitta
D045744:Cell Line, Tumor; D002952:Citric Acid Cycle / Q000235:genetics*; D004734:Energy Metabolism; D005947:Glucose / Q000378:metabolism; D005973:Glutamine / Q000235:genetics / Q000378:metabolism*; D005978:Glutathione / Q000378:metabolism; D006019:Glycolysis; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D058990:Molecular Targeted Therapy; D010084:Oxidation-Reduction
D005973:Glutamine; D005978:Glutathione; D005947:Glucose
AML; Anaplerosis; Glutamine; Glutathione; TCA cycle