title: The Ketogenic Diet Does Not Affect Growth of Hedgehog Pathway Medulloblastoma in Mice.
abstract: 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.
authors.affiliation: Department of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, United States of America.
authors.forename: Mai T
authors.initials: MT
authors.lastname: Dang
authors.affiliation: Department of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, United States of America.
authors.forename: Suzanne
authors.initials: S
authors.lastname: Wehrli
authors.affiliation: Abramson Cancer Center, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
authors.forename: Chi V
authors.initials: CV
authors.lastname: Dang
authors.affiliation: Department of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, United States of America.
authors.forename: Tom
authors.initials: T
authors.lastname: Curran
mesh_terms: D000813:Anilides / Q000494:pharmacology; D000818:Animals; D015153:Blotting, Western; D002528:Cerebellar Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D055423:Diet, Ketogenic; D006019:Glycolysis; D053823:Hedgehog Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D006593:Hexokinase / Q000378:metabolism; D007328:Insulin / Q000378:metabolism; D008279:Magnetic Resonance Imaging; D008527:Medulloblastoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D018345:Mice, Knockout; D016513:Mice, SCID; D000072079:Patched Receptors; D011725:Pyridines / Q000494:pharmacology; D011956:Receptors, Cell Surface / Q000172:deficiency / Q000235:genetics; D015398:Signal Transduction; D016019:Survival Analysis; D047368:Tumor Burden / Q000187:drug effects / Q000235:genetics; D016159:Tumor Suppressor Protein p53 / Q000172:deficiency / Q000235:genetics
chemical_list: D000813:Anilides; D053823:Hedgehog Proteins; C538724:HhAntag691; D007328:Insulin; D000072079:Patched Receptors; D011725:Pyridines; D011956:Receptors, Cell Surface; D016159:Tumor Suppressor Protein p53; D006593:Hexokinase; C000598049:hexokinase 2, mouse