Format

Send to

Choose Destination
Oncotarget. 2017 Jul 17;8(34):57201-57215. doi: 10.18632/oncotarget.19306. eCollection 2017 Aug 22.

The ketogenic diet is not feasible as a therapy in a CD-1 nu/nu mouse model of renal cell carcinoma with features of Stauffer's syndrome.

Author information

1
Laura Bassi Centre of Expertise-THERAPEP, Research Program for Receptor Biochemistry and Tumor Metabolism, Department of Pediatrics, Paracelsus Medical University, Salzburg, Austria.
2
Department of Pharmacy and Biotechnology (FABIT), University of Bologna, Bologna, Italy.
3
Clinical Nutrition, Vitaflo International Ltd, Liverpool, UK.
4
Department of Laboratory Medicine, Paracelsus Medical University, Salzburg, Austria.
5
Department of Pediatrics, Paracelsus Medical University, Salzburg, Austria.

Abstract

The ketogenic diet (KD), a high-fat low-carbohydrate diet, has shown some efficacy in the treatment of certain types of tumors such as brain tumors and neuroblastoma. These tumors are characterized by the Warburg effect. Because renal cell carcinoma (RCC) presents similar energetic features as neuroblastoma, KD might also be effective in the treatment of RCC. To test this, we established xenografts with RCC 786-O cells in CD-1 nu/nu mice and then randomized them to a control diet or to KDs with different triglyceride contents. Although the KDs tended to reduce tumor growth, mouse survival was dramatically reduced due to massive weight loss. A possible explanation comes from observations of human RCC patients, who often experience secondary non-metastatic hepatic dysfunction due to secretion of high levels of inflammatory cytokines by the RCCs. Measurement of the mRNA levels of tumor necrosis factor alpha (TNFα) and interleukin-6 revealed high expression in the RCC xenografts compared to the original 786-O cells. The expression of TNFα, interleukin-6 and C-reactive protein were all increased in the livers of tumor-bearing mice, and KD significantly boosted their expression. KDs did not cause weight loss or liver inflammation in healthy mice, suggesting that KDs are per se safe, but might be contraindicated in the treatment of RCC patients presenting with Stauffer's syndrome, because they potentially worsen the associated hepatic dysfunction.

KEYWORDS:

Warburg effect; ketogenic diet; metabolism; mitochondria; renal cell carcinoma

Supplemental Content

Full text links

Icon for Impact Journals, LLC Icon for PubMed Central
Loading ...
Support Center