The Metabolism of Tumors

Warburn, Otto; Dickens, F.

doi:10.1097/00000441-193107000-00022

Cited by 356 publications

(260 citation statements)

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“…The incidence of premalignant pathologies (intraductal proliferation and ductal carcinoma in situ) was also significantly reduced by both doses of 2-DG and the average number of these pathologies per rat was also reduced, but that reduction was not statistically significant. Collectively, these data suggest that perturbing intracellular metabolism of glucose acts at an early stage in the disease process as would be predicted based on evidence that energy production in transformed cells switches primarily to glycolysis, the Warberg effect, and that this switch is induced by oncogene activation and/ or loss of tumor suppressor gene function (12,13,32).…”

Section: Discussionmentioning

confidence: 74%

2-Deoxyglucose as an Energy Restriction Mimetic Agent: Effects on Mammary Carcinogenesis and on Mammary Tumor Cell Growth In vitro

et al. 2005

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Dietary energy restriction (DER) is a potent inhibitor of carcinogenesis, but chronic DER in human populations is difficult to sustain. Consequently, interest exists in identifying energy restriction mimetic agents (ERMAs), agents that provide the health benefits of DER without reducing caloric intake. The selection of a candidate ERMAs for this study was based on evidence that DER inhibits carcinogenesis by limiting glucose availability. The study objective was to determine if 2-deoxyglucose (2-DG), a glucose analogue that blocks its metabolism, would inhibit mammary carcinogenesis. Pilot studies were done to establish a dietary concentration of 2-DG that would not affect growth. For the carcinogenesis study, ninety 21-day-old female Sprague-Dawley rats were injected i.p. with 50 mg of 1-methyl-1-nitrosourea per kilogram of body weight. Following injection, animals were ad libitum fed AIN-93G diet containing 0.00%, 0.02%, or 0.03% (w/w) 2-DG for 5 weeks. 2-DG decreased the incidence and multiplicity of mammary carcinomas and prolonged cancer latency (P < 0.05). The 0.02% dose of 2-DG had no effect on circulating levels of glucose, insulin, insulin-like growth factor-I, IGF binding protein-3, leptin, or body weight gain. Using MCF-7 human breast cancer cells to investigate the signaling pathways perturbed by disruption of glucose metabolism, 2-DG reduced cell growth and intracellular ATP in a dose-and timedependent manner (P < 0.01). Treatment with 2-DG increased levels of phosphorylated AMP-activated protein kinase and Sirt-1 and reduced phosphorylated Akt (P < 0.05). These studies support the hypothesis that DER inhibits carcinogenesis, in part, by limiting glucose availability and that energy metabolism is a target for the development of ERMA for chemoprevention. (Cancer Res 2005; 65(15): 7023-30)

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Section: Discussionmentioning

confidence: 74%

2-Deoxyglucose as an Energy Restriction Mimetic Agent: Effects on Mammary Carcinogenesis and on Mammary Tumor Cell Growth In vitro

et al. 2005

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“…Even when glucose was omitted from the perfusate, there was no detectable incorporation of acetate carbons into TCA cycle intermediates. Incubation with labeled acetate alone (no glucose or glutamine) was not examined, as the 31 P studies had shown that spheroids were not stable under these conditions for more than a few hours (see above).…”

Section: Labeling Metabolic Intermediatesmentioning

confidence: 99%

Metabolism of alternative substrates and the bioenergetic status of EMT6 tumor cell spheroids

Wehrle

McGovern

et al. 2000

NMR Biomed.

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“…This characteristic was recognized several decades ago 41 (Figure 3). The glycolytic flow can be inhibited by the substance 2-deoxyglucose, which is a glucose analogue (Figure 4).…”

Section: Manipulation Of Glucose Metabolismmentioning

confidence: 82%

Ischaemic and Metabolic Treatment of Hepatic Tumours

Åhrén

Bengmark

1988

HPB Surgery

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For treatment of malignancies, physical and metabolic differences between tumour cells and host cells have guided the development of new approaches. In this review, two new approaches to be used in the treatment of liver malignancies are outlined: ischaemic therapy and interferences with the glucose metabolism. Ischaemic therapy of liver malignancies has been used in different forms during the last 20 years: from ligation of the hepatic artery, embolization of the arterial tree, transient occlusion of the hepatic artery to the present day use of temporary, intermittent, transient hepatic arterial occlusion. The beneficial effect of ischaemic therapy on malignancies is supposed to depend on oxygen and nutritional deficiency, formation of oxygen-derived free radicals and loss of function in cellular enzymes. The tumour cells seem thereby to be more sensitive than the host cells. Also, ischaemia might potentiate the effect of cytotoxic drugs. Intereferencies with glucose metabolism might be directed either towards the exaggerated tumour glycolysis, for example by glucose analogues like 2-deoxy-glucose, or towards the exaggerated host gluconeogenesis, for example by hydrazine sulphate. These treatments result in reduction of the glucose availability in the intracellular glucose metabolism in the tumour cells and have experimentally been demonstrated to be correlated to reduced tumour growth. It is concluded that both these approaches, ischaemic therapy and manipulations with the glucose metabolism, seem promising for the future. What is needed now is research to clarify the mechanims behind the effects, to establish their full consequences, and to identify the clinical use of these treatments and their possible combinations.

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The Metabolism of Tumors

Cited by 356 publications

References 0 publications

2-Deoxyglucose as an Energy Restriction Mimetic Agent: Effects on Mammary Carcinogenesis and on Mammary Tumor Cell Growth In vitro

2-Deoxyglucose as an Energy Restriction Mimetic Agent: Effects on Mammary Carcinogenesis and on Mammary Tumor Cell Growth In vitro

Metabolism of alternative substrates and the bioenergetic status of EMT6 tumor cell spheroids

Ischaemic and Metabolic Treatment of Hepatic Tumours

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