Growth of xenotransplanted leukemia cells is influenced by diet nutrients and is attenuated with 2-deoxyglucose.

We examined the effects of diet nutrients on xenotransplanted leukemia cells, THP-1 or NB4. THP-1 tumors showed more growth when fed with high fat diet, while NB4 tumors grew more with high carbohydrate diet. Then, administration of 2-deoxyglucose (a glycolysis inhibitor) showed a significant antitumor effect on both tumors: NB4 tumor showed large necrotic areas, while THP-1 tumor did not, but had augmented expression of enzymes for fatty acid oxidation. 2-Deoxyglucose inhibited the growth of NB4 by cell death because main energy producing pathway (glycolysis) was abolished, while 2-deoxyglucose slowed the growth of THP-1 by shifting energy metabolism to fatty acid β-oxidation.

Tsunekawa-Imai N ，Miwa H ，Shikami M ，Suganuma K ，Goto M ，Mizuno S ，Takahashi M ，Mizutani M ，Horio T ，Komatsubara H ，Gotou M ，Yamamoto H ，Wakabayashi M ，Watarai M ，Hanamura I ，Imamura A ，Mihara H ，Nitta M ... -  《-》

Energy metabolism of leukemia cells: glycolysis versus oxidative phosphorylation.

Suganuma K ，Miwa H ，Imai N ，Shikami M ，Gotou M ，Goto M ，Mizuno S ，Takahashi M ，Yamamoto H ，Hiramatsu A ，Wakabayashi M ，Watarai M ，Hanamura I ，Imamura A ，Mihara H ，Nitta M ... -  《-》

Leukemia cells demonstrate a different metabolic perturbation provoked by 2-deoxyglucose.

Miwa H ，Shikami M ，Goto M ，Mizuno S ，Takahashi M ，Tsunekawa-Imai N ，Ishikawa T ，Mizutani M ，Horio T ，Gotou M ，Yamamoto H ，Wakabayashi M ，Watarai M ，Hanamura I ，Imamura A ，Mihara H ，Nitta M ... -  《-》

ENO2 Promotes Cell Proliferation, Glycolysis, and Glucocorticoid-Resistance in Acute Lymphoblastic Leukemia.

The metabolic features of cancer cells have long been acknowledged to be altered and to provide new therapeutic opportunities. The expression of glycolytic enzyme enolase 2 (ENO2) was found to be closely associated with the clinical features of acute lymphoblastic leukemia (ALL) patients, but its functions remain unclear in ALL. We evaluated the association between ENO2 mRNA expression in bone marrow mononuclear cells (BM-MNCs) and the efficacy of chemotherapy, and further explored the function of ENO2 in ALL. The molecular mechanisms of ENO2 expression and its effects on cell growth, glycolysis and glucocorticoid resistance were explored by Cell Counting Kit-8, glucose-consumption assay, Quantitative RT-PCR, Western blotting and in vivo tumorigenesis in NOD/SCID mice. The results showed that ENO2 mRNA expression in BM-MNCs was significantly decreased when patients completed induction chemotherapy and reached complete remission (CR). ENO2 mRNA expression was increased when patients suffered relapse. Functional studies demonstrated that ENO2 promoted cell growth, glycolysis, and glucocorticoid resistance, all of which were effectively inhibited when ENO2 was silenced with shRNAs. Further studies revealed that ENO2 up-regulated various glycolysis-related genes and enhanced Akt activity with subsequent glycogen synthase kinase3β (GSK-3β) phosphorylation, inducing cell proliferation and glycolysis. The combination of silencing ENO2 and 2-deoxyglucose (2-DG) synergistically inhibited leukemia cell survival. These results indicate that ENO2 may be a biological marker for monitoring chemotherapeutic efficacy and relapse in ALL. ENO2 may provide a potential therapeutic strategy for ALL.

Liu CC ，Wang H ，Wang WD ，Wang L ，Liu WJ ，Wang JH ，Geng QR ，Lu Y ... -  《-》

2-Deoxyglucose as an energy restriction mimetic agent: effects on mammary carcinogenesis and on mammary tumor cell growth in vitro.

Zhu Z ，Jiang W ，McGinley JN ，Thompson HJ ... -  《CANCER RESEARCH》