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Some Leukemia Cells Are Dependent on Glutamine as Energy Source

Authors :
Masato Shikami
Masakazu Nitta
Miyuki Takahashi
Hiroshi Miwa
Mineaki Goto
Norikazu Imai
Shohei Mizuno
Kazuto Suganuma
Source :
Blood. 116:4861-4861
Publication Year :
2010
Publisher :
American Society of Hematology, 2010.

Abstract

Abstract 4861 In cancer cells, glucose uptake is elevated and glycolysis persists even under aerobic conditions (Warburg effect). Glutamine metabolism is another target for alteration in cancer development. Glutaminolysis (catabolism of glutamine to generate ATP) is known to increase in tumors. We examined the dependency of the leukemia cells (Kasumi-1, THP-1, HL-60 and NB4) on glucose or glutamine by measuring the growth (MTS count) in glucose- or glutamine-deprived condition. Glucose withdrawal greatly suppressed the growth of all 4 cell lines. However, glutamine withdrawal showed different growth suppressive effects among the cell lines (Kasumi-1: 55% of control, THP-1: 60%, HL-60: 39%, NB4: 70%). HL-60 was most sensitive to glutamine deprivation. The growth suppression of HL-60 due to glutamine withdrawal was partially rescued by oxaloacetate (OAA), a TCA cycle metabolite, while the growth of other cell lines was not rescued by OAA. In the course of glutamine catabolism, ammonia is liberated. Although basal level of the ammonia concentration was not so different among each cell line, glycolysis inhibitor (2-deoxyglucose) treatment enhanced the ammonia generation in HL-60 (Kasumi-1: 2.8% increased, THP-1: 1.7%, HL-60: 6.1%, NB4: 2.8%). Glutaminase, an enzyme converting glutamine to glutamate, is most abundantly expressed in HL-60 in western blot analysis. In addition, HL-60 was most sensitive to the treatment with aminooxyacetate, an inhibitor of glutamate-dependent transaminases that convert glutamate into a-ketoglutarate in the glutaminolytic pathway (Kasumi-1: 86% of control, THP-1: 97%, HL-60: 79%, NB4: 83%). Taken together, HL-60 was considered as glutamine dependent cell line. Therapies targeting glutamine metabolism, such as glutamine depletion or use of inhibitor of glutaminolytic pathway, might be effective against some leukemia. Disclosures: No relevant conflicts of interest to declare.

Details

ISSN :
15280020 and 00064971
Volume :
116
Database :
OpenAIRE
Journal :
Blood
Accession number :
edsair.doi...........60d8eb4d417b7635eadd113895c857ea
Full Text :
https://doi.org/10.1182/blood.v116.21.4861.4861