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

Poff, A.M. ; Ari, C. ; Arnold, P. ; Seyfried, T.N. ; D'Agostino, D.P.

International journal of cancer, 2014-10, Vol.135 (7), p.1711-1720 [Periódico revisado por pares]

Hoboken, NJ: Wiley-Blackwell

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  • Título:
    Ketone supplementation decreases tumor cell viability and prolongs survival of mice with metastatic cancer
  • Autor: Poff, A.M. ; Ari, C. ; Arnold, P. ; Seyfried, T.N. ; D'Agostino, D.P.
  • Assuntos: Animals ; Apoptosis ; Biological and medical sciences ; Blood Glucose - analysis ; Body Weight ; Brain Neoplasms - diet therapy ; Brain Neoplasms - mortality ; Brain Neoplasms - secondary ; Cancer ; Cancer Therapy ; Cell Proliferation ; Dietary Supplements ; Glucose ; Humans ; ketone ; Ketones - administration & dosage ; Luminescent Measurements ; Male ; Medical research ; Medical sciences ; Metastasis ; Mice ; Multiple tumors. Solid tumors. Tumors in childhood (general aspects) ; Rodents ; Survival Rate ; Tumor Cells, Cultured ; Tumors ; Warburg effect
  • É parte de: International journal of cancer, 2014-10, Vol.135 (7), p.1711-1720
  • Notas: Conflicts of interest
    Patent 12B152PRWO; University of South Florida; D.P. D'Agostino, A. Poff, P. Arnold, “Targeting cancer with metabolic therapy and hyperbaric oxygen.” P. Arnold (Savind Inc.) has received financial support (ONR N000140910244) from D. D'Agostino (USF) to synthesize ketone esters. The remaining authors have no conflicts of interest
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    Grant sponsor: Scivation Inc
    Conflicts of interest: Patent 12B152PRWO; University of South Florida; D.P. D’Agostino, A. Poff, P. Arnold, “Targeting cancer with metabolic therapy and hyperbaric oxygen.” P. Arnold (Savind Inc.) has received financial support (ONR N000140910244) from D. D’Agostino (USF) to synthesize ketone esters. The remaining authors have no conflicts of interest
  • Descrição: 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. What's New? Unlike healthy tissues, cancer cells cannot efficiently process ketone bodies for energy. Ketones also slow the proliferation of tumor cells. These authors speculated that dietary ketones might halt metastasis. They injected metastatic cancer cells into mice, and then fed them a diet supplemented with ketones. The mice receiving the supplements outlived the mice who did not get the ketone‐enriched diet, suggesting that this strategy is worth pursuing further.
  • Editor: Hoboken, NJ: Wiley-Blackwell
  • Idioma: Inglês
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  • Realização: ABCD-USP USP   Logos de Redes Sociais: Freepik

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