The Inhibition of Malignant Cell Growth by Ketone Bodies

Magee, Barbara A; Potezny, N.; Rofe, Allan M.; Conyers, R. A. J.

doi:10.1038/icb.1979.54

Cited by 95 publications

(84 citation statements)

References 8 publications

(14 reference statements)

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“…These findings give support for parenteral nutrition studies in the wasted cancer patient where some consideration is now being given to the parenteral infusion of lipid, rather than glucose, with potential benefits in the maintenance of body weight and lack of tumour progression (Magee et al, 1979;Conyers et al, 1979b;Buzby et al, 1980;Brennan, 1981).…”

Section: Blood and Liver Metabolitesmentioning

confidence: 85%

“…In other studies with these mice, increased ketonaemia was observed in both TB and NTB mice when fed either medium-or long-chain tryglyceride (Magee et al, 1979;Carman et al, 1981), which suggests that the ketogenic capacity of the liver in this model is not decreased by the presence of the tumour. PQ present study precluded the assessment of circulating fatty acid concentrations.…”

Section: Blood and Liver Metabolitesmentioning

confidence: 97%

“…However, in earlier studies, we have shown that if either fasted cancer patients or tumour-bearing mice (Magee et al, 1979;Conyers et al, 1979bConyers et al, , 1982Carman et al, 1981) are given an exogenous supply of fatty acids (parenteral or oral), marked ketonaemia is observed, suggesting that the ability of the liver to make ketone bodies is not compromised. Other studies indicate that tumour-bearing patients retain the ability to produce ketone bodies when fasted (Schein et al, 1979;Axelrod et al, 1983).…”

mentioning

confidence: 99%

“…In starvation, the increased blood concentration of ketone bodies provides an alternative fuel to glucose, inhibits glucose utilization and acts to limit proteolysis and lipolysis (Cahill, 1976;Sherwin et al, 1975;Robinson and Williamson, 1980). It is clear that the wasting seen in association with cancer is different from uncomplicated starvation (Stein, 1978;Conyers et al, 1979a,b;Magee et al, 1979;Brennan, 1981) but little is known about the role of ketone bodies in this state. The host's ability to become ketonaemic may well influence his survival in terms of energy conservation, as in uncomplicated starvation, and decreased tumour progression due to either the inability of tumours to use ketone bodies as fuels or the inhibitory effects of ketone bodies on malignant cell growth (Conyers et al, 1979a;Magee et al, 1979;Tisdale & Brennan, 1983).…”

mentioning

confidence: 99%

“…Biochemicals All enzymes and biochemicals were purchased from Boehringer Mannheim, Australia. The sources of culture material used to grow the B16 melanoma have been described previously (Magee et al, 1979 …”

mentioning

confidence: 99%

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The metabolic response of tumour-bearing mice to fasting

Rofe¹,

Porter²,

Bais³

et al. 1985

Br J Cancer

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Summary The suggestion that the ketonaemic response to fasting may be altered in the tumour-bearing state was investigated by studying the metabolism of fasted C57/BL6j mice bearing transplanted B16 melanomas. Ketone body (D-3-hydroxybutyrate and acetoacetate) concentrations in the blood of the tumour-bearing mice were significantly increased after a 24h fast compared to control mice with identical dietary histories. Hepatic glycogen levels were lower at the start of the fasting period in the tumour-bearing mice as were the fat stores. The loss of adipose tissue during the fasting period was greater in the tumour-bearing mice. After 48 h of fasting, the ketonaemia was significantly lower in the tumour-bearing mice compared to the appropriate controls. Two distinct metabolic states are indicated in these fasted tumour-bearing mice, one characterised by accelerated ketonaemia, and a later, near terminal stage, where fat deposits are markedly depleted and ketonaemia is decreased.

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Section: Blood and Liver Metabolitesmentioning

confidence: 85%

Section: Blood and Liver Metabolitesmentioning

confidence: 97%

mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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The metabolic response of tumour-bearing mice to fasting

Rofe¹,

Porter²,

Bais³

et al. 1985

Br J Cancer

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Ketone supplementation decreases tumor cell viability and prolongs survival of mice with metastatic cancer

Poff

Ari

Arnold³

et al. 2014

Intl Journal of Cancer

168

164

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Cancer cells express an abnormal metabolism characterized by increased glucose consumption owing to genetic mutations and mitochondrial dysfunction. Previous studies indicate that unlike healthy tissues, cancer cells are unable to effectively use ketone bodies for energy. Furthermore, ketones inhibit the proliferation and viability of cultured tumor cells. As the Warburg effect is especially prominent in metastatic cells, we hypothesized that dietary ketone supplementation would inhibit metastatic cancer progression in vivo. Proliferation and viability were measured in the highly metastatic VM-M3 cells cultured in the presence and absence of β-hydroxybutyrate (βHB). Adult male inbred VM mice were implanted subcutaneously with firefly luciferase-tagged syngeneic VM-M3 cells. Mice were fed a standard diet supplemented with either 1,3-butanediol (BD) or a ketone ester (KE), which are metabolized to the ketone bodies βHB and acetoacetate. Tumor growth was monitored by in vivo bioluminescent imaging. Survival time, tumor growth rate, blood glucose, blood βHB and body weight were measured throughout the survival study. Ketone supplementation decreased proliferation and viability of the VM-M3 cells grown in vitro, even in the presence of high glucose. Dietary ketone supplementation with BD and KE prolonged survival in VM-M3 mice with systemic metastatic cancer by 51 and 69%, respectively (p < 0.05). Ketone administration elicited anticancer effects in vitro and in vivo independent of glucose levels or calorie restriction. The use of supplemental ketone precursors as a cancer treatment should be further investigated in animal models to determine potential for future clinical use.

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