Non-Toxic Metabolic Management of Metastatic Cancer in VM Mice: Novel Combination of Ketogenic Diet, Ketone Supplementation, and Hyperbaric Oxygen Therapy

• Published in: PloS one Vol. 10; no. 6; p. e0127407
• Main Authors: Poff, A M, Ward, N, Seyfried, T N, Arnold, P, D'Agostino, D P
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 10.06.2015; Public Library of Science (PLoS)
• Subjects: Angiogenesis; Animals; Biomedical research; Brain cancer; Cancer; Cancer metastasis; Cancer therapies; Carbohydrates; Cell culture; Cell proliferation; Diet; Diet, Ketogenic; Dietary supplements; Fermentation; Glucose; Growth rate; Health aspects; High fat diet; Hyperbaric oxygen therapy; Hyperbaric Oxygenation; Hypoxia; Ketogenesis; Ketones; Ketones - administration & dosage; Laboratories; Low carbohydrate diet; Medical prognosis; Metabolism; Metastases; Metastasis; Mice; Neoplasm Metastasis - therapy; Neoplasms, Experimental - pathology; Nutrition research; Oxygen; Oxygen therapy; Pharmacology; Phenotypes; Physiology; Researchers; Supplementation; Therapy; Tumors; Viability; Florida; United States > US
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0127407

The Warburg effect and tumor hypoxia underlie a unique cancer metabolic phenotype characterized by glucose dependency and aerobic fermentation. We previously showed that two non-toxic metabolic therapies - the ketogenic diet with concurrent hyperbaric oxygen (KD+HBOT) and dietary ketone supplementation - could increase survival time in the VM-M3 mouse model of metastatic cancer. We hypothesized that combining these therapies could provide an even greater therapeutic benefit in this model. Mice receiving the combination therapy demonstrated a marked reduction in tumor growth rate and metastatic spread, and lived twice as long as control animals. To further understand the effects of these metabolic therapies, we characterized the effects of high glucose (control), low glucose (LG), ketone supplementation (βHB), hyperbaric oxygen (HBOT), or combination therapy (LG+βHB+HBOT) on VM-M3 cells. Individually and combined, these metabolic therapies significantly decreased VM-M3 cell proliferation and viability. HBOT, alone or in combination with LG and βHB, increased ROS production in VM-M3 cells. This study strongly supports further investigation into this metabolic therapy as a potential non-toxic treatment for late-stage metastatic cancers.