Oncotarget

Research Papers:

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

Silvia Vidali, Sepideh Aminzadeh-Gohari, René Günther Feichtinger, Renaud Vatrinet, Andreas Koller, Felix Sternberg, Tricia Rutherford, Maura O’Donnell, Andrea Stöger-Kleiber, Bridget Lambert, Thomas Klaus Felder, Wolfgang Sperl and Barbara Kofler _

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Oncotarget. 2017; 8:57201-57215. https://doi.org/10.18632/oncotarget.19306

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Abstract

Silvia Vidali1, Sepideh Aminzadeh-Gohari1, René Günther Feichtinger1, Renaud Vatrinet2, Andreas Koller1, Felix Sternberg1, Tricia Rutherford3, Maura O’Donnell3, Andrea Stöger-Kleiber3, Bridget Lambert3, Thomas Klaus Felder4, Wolfgang Sperl5 and Barbara Kofler1

1Laura Bassi Centre of Expertise-THERAPEP, Research Program for Receptor Biochemistry and Tumor Metabolism, Department of Pediatrics, Paracelsus Medical University, Salzburg, Austria

2Department of Pharmacy and Biotechnology (FABIT), University of Bologna, Bologna, Italy

3Clinical Nutrition, Vitaflo International Ltd, Liverpool, UK

4Department of Laboratory Medicine, Paracelsus Medical University, Salzburg, Austria

5Department of Pediatrics, Paracelsus Medical University, Salzburg, Austria

Correspondence to:

Barbara Kofler, email: [email protected]

Keywords: renal cell carcinoma, mitochondria, ketogenic diet, metabolism, Warburg effect

Received: March 10, 2017     Accepted: June 27, 2017     Published: July 17, 2017

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.


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