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Enhancement of Cancer Therapy Using Ketogenic Diet

Part of the Oxidative Stress in Applied Basic Research and Clinical Practice book series (OXISTRESS)

Abstract

Ketogenic diets, which are low in protein and carbohydrates and high in fats, result in elevated ketones (β-hydroxybuturate and acetoacetate; precursors to Acetyl-CoA) forcing cells to rely more heavily on mitochondrial metabolism for energy production. It has been hypothesized that cancer cells, relative to normal cells, exist in a condition of chronic metabolic oxidative stress mediated by O •−2 and H2O2, with a major site of pro-oxidant production being mitochondrial electron transport chain complexes. If cancer cells (relative to normal cells) have defective mitochondrial O2 metabolism that results in chronic metabolic oxidative stress and ketogenic diets forcing cancer cells to rely more heavily on mitochondrial O2 metabolism, then ketogenic diets would be expected to selectively cause oxidative stress in cancer cells. The increased steady-state level of oxidative stress in turn would be expected to selectively sensitize cancer cells to conventional cancer therapeutic agents that cause cell killing via oxidative stress. The current study demonstrates that a ketogenic diet increases parameters indicative of oxidative stress, as demonstrated by an increase in oxidized proteins in the plasma of mice fed a ketogenic diet, and also sensitizes FaDu head and neck cancer xenograft tumors to the antitumor effects of cisplatin. These results support the hypothesis that ketogenic diets may be useful adjuvants for improving outcomes with cisplatin in head and neck cancer therapy.

Keywords

  • Ketogenic Diet
  • Protein Carbonyl Content
  • Systemic Oxidative Stress
  • Sensitize Cancer Cell
  • Standard Rodent Diet

These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Acknowledgments

This work was initially supported by gifts from Ms. Marie Foster with matching funds from IBM, Ms. Nellie K. Spitz, and Douglas R. Spitz Sr. as well as NIH grants R21CA139182, R01CA133114, and T32CA078586.

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Correspondence to Melissa A. Fath PhD .

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Fath, M.A., Simons, A.L., Erickson, J., Anderson, M.E., Spitz, D.R. (2012). Enhancement of Cancer Therapy Using Ketogenic Diet. In: Spitz, D., Dornfeld, K., Krishnan, K., Gius, D. (eds) Oxidative Stress in Cancer Biology and Therapy. Oxidative Stress in Applied Basic Research and Clinical Practice. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-61779-397-4_3

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