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Oncotarget. 2017 Aug 8;8(39):64728-64744. doi: 10.18632/oncotarget.20041. eCollection 2017 Sep 12.

A ketogenic diet supplemented with medium-chain triglycerides enhances the anti-tumor and anti-angiogenic efficacy of chemotherapy on neuroblastoma xenografts in a CD1-nu mouse model.

Author information

1
Department of Pediatrics, Laura Bassi Centre of Expertise-THERAPEP, Research Program for Receptor Biochemistry and Tumor Metabolism, Paracelsus Medical University, Salzburg, Austria.
2
Clinical Nutrition Vitaflo International, Liverpool, United Kingdom.
3
Department of Pediatrics, Paracelsus Medical University, Salzburg, Austria.

Abstract

Neuroblastoma (NB) is a pediatric malignancy characterized by a marked reduction in aerobic energy metabolism. Recent preclinical data indicate that targeting this metabolic phenotype by a ketogenic diet (KD), especially in combination with calorie restriction, slows tumor growth and enhances metronomic cyclophosphamide (CP) therapy of NB xenografts. Because calorie restriction would be contraindicated in most cancer patients, the aim of the present study was to optimize the KD such that the tumors are sensitized to CP without the need of calorie restriction. In a NB xenograft model, metronomic CP was combined with KDs of different triglyceride compositions and fed to CD1-nu mice ad libitum. Metronomic CP in combination with a KD containing 8-carbon medium-chain triglycerides exerted a robust anti-tumor effect, suppressing growth and causing a significant reduction of tumor blood-vessel density and intratumoral hemorrhage, accompanied by activation of AMP-activated protein kinase in NB cells. Furthermore, the KDs caused a significant reduction in the serum levels of essential amino acids, but increased those of serine, glutamine and glycine. Our data suggest that targeting energy metabolism by a modified KD may be considered as part of a multimodal treatment regimen to improve the efficacy of classic anti-NB therapy.

KEYWORDS:

Warburg effect; ketogenic diet; medium-chain triglycerides; neuroblastoma

Conflict of interest statement

CONFLICTS OF INTEREST Tricia Rutherford, Maura O’Donnel, Andrea Stöger-Kleiber are employees of Vitaflo International and therefore have a potential financial conflict of interest. The other authors declare they have no conflicts of interest.

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