Ketone supplementation decreases tumor cell viability and prolongs survival of mice with metastatic cancer
Authors: C Ari
A M Poff
D P D&#x27;Agostino
T N Seyfried
P Arnold
Journal: International Journal of Cancer (2014)
Discipline: CLINICAL MEDICINE
Keywords: Warburg effect; ketone; metastasis.
Affiliations: Department of Molecular Pharmacology and Physiology, Morsani College of Medicine, Hyperbaric Biomedical Research Laboratory, University of South Florida, Tampa, FL., Department of Molecular Pharmacology and PhysiologyMorsani College of MedicineHyperbaric Biomedical Research LaboratoryUniversity of South FloridaTampa FL, Savind, Inc.Seymour IL, Department of BiologyBoston CollegeChestnut Hill MA

Abstract:  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 &lt; 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. 

Retracted: No

PubPeer comments:
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 https: www.cellphysiolbiochem.com Articles ER E2016MS701 , 
 #3 Erratum. https: www.cellphysiolbiochem.com Articles 000257 PDF 000257.pdf In the original article by Zhang, et al., entitled u201cCerebral Mast Cells Participate In Postoperative Cognitive Dysfunction by Promoting Astrocyte Activationu201d [Cell Physiol Biochem 2016;40(1-2):104-116, DOI: 10.1159 000452528], in Figure 1 the picture of mast cell tryptase immunostaining in Cro+sur (3 days) group is incorrect. During the process of image synthesis, the authors mixed the pictures of Sur (1 day) group and Cro+sur (3 days) group, leading to the duplicate between them. The correct Fig. 1 is displayed below. The authors confirm that all of the results and conclusions of the article remain unchanged, as well as the figure legend. The authors sincerely apologize for this mistake. ![] ,