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

A M Poff; N Ward; T N Seyfried; P Arnold; D P D'Agostino

doi:10.1371/journal.pone.0127407

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

PLoS One. 2015 Jun 10;10(6):e0127407. doi: 10.1371/journal.pone.0127407. eCollection 2015.

Authors

A M Poff¹, N Ward¹, T N Seyfried², P Arnold³, D P D'Agostino¹

Affiliations

¹ Department of Molecular Pharmacology and Physiology, Morsani College of Medicine, Hyperbaric Biomedical Research Laboratory, University of South Florida, Tampa, Florida, United States of America.
² Department of Biology, Boston College, Chestnut Hill, Massachusetts, United States of America.
³ Savind, Inc. Seymour, Illinois, United States of America.

Abstract

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Diet, Ketogenic*
Hyperbaric Oxygenation*
Ketones / administration & dosage*
Mice
Neoplasm Metastasis / therapy*
Neoplasms, Experimental / pathology*

Substances

Ketones

Grants and funding

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. Funding for this project was supported in part by a charitable contribution from Scivation, Inc.; however, the company did not influence study design, data collection, analysis, or interpretation of results. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.