The Ketogenic Diet Does Not Affect Growth of Hedgehog Pathway Medulloblastoma in Mice

• Published in: PloS one 2015-07, Vol.10 (7), p.e0133633-e0133633
• Main Authors: Dang, Mai T, Wehrli, Suzanne, Dang, Chi V, Curran, Tom
• Format: Article
• Language: English
• Subjects: 1-Phosphatidylinositol 3-kinase; Alzheimer's disease; Alzheimers disease; Anilides - pharmacology; Animals; Blotting, Western; Brain; Brain cancer; Brain tumors; Cancer; Cancer therapies; Carbohydrates; Cerebellar Neoplasms - genetics; Cerebellar Neoplasms - metabolism; Cerebellar Neoplasms - pathology; Children; Diet; Diet, Ketogenic; Genetic engineering; Genetically modified organisms; Glycolysis; Growth; Health aspects; Hedgehog protein; Hedgehog Proteins - antagonists & inhibitors; Hedgehog Proteins - metabolism; Hexokinase - metabolism; High fat diet; Hospitals; Insulin; Insulin - metabolism; Ketogenesis; Kinases; Laboratory animals; Low carbohydrate diet; Magnetic Resonance Imaging; Medical research; Medulloblastoma; Medulloblastoma - genetics; Medulloblastoma - metabolism; Medulloblastoma - pathology; Metabolism; Mice; Mice, 129 Strain; Mice, Inbred C57BL; Mice, Inbred NOD; Mice, Knockout; Mice, SCID; Mutation; Oxygen; Patched Receptors; Pathology; Pediatrics; Physiological aspects; Prostate cancer; Pyridines - pharmacology; Receptors, Cell Surface - deficiency; Receptors, Cell Surface - genetics; Rodents; Signal Transduction; Survival Analysis; Tumor Burden - drug effects; Tumor Burden - genetics; Tumor Suppressor Protein p53 - deficiency; Tumor Suppressor Protein p53 - genetics; Tumors
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0133633

The altered metabolism of cancer cells has long been viewed as a potential target for therapeutic intervention. In particular, brain tumors often display heightened glycolysis, even in the presence of oxygen. A subset of medulloblastoma, the most prevalent malignant brain tumor in children, arises as a consequence of activating mutations in the Hedgehog (HH) pathway, which has been shown to promote aerobic glycolysis. Therefore, we hypothesized that a low carbohydrate, high fat ketogenic diet would suppress tumor growth in a genetically engineered mouse model of medulloblastoma. However, we found that the ketogenic diet did not slow the growth of spontaneous tumors or allograft flank tumors, and it did not exhibit synergy with a small molecule inhibitor of Smoothened. Serum insulin was significantly reduced in mice fed the ketogenic diet, but no alteration in PI3 kinase activity was observed. These findings indicate that while the ketogenic diet may be effective in inhibiting growth of other tumor types, it does not slow the growth of HH-medulloblastoma in mice.