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Ketogenic diets slow melanoma growth in vivo regardless of tumor genetics and metabolic plasticity.
Weber, Daniela D; Aminzadeh-Gohari, Sepideh; Thapa, Maheshwor; Redtenbacher, Anna-Sophia; Catalano, Luca; Capelôa, Tânia; Vazeille, Thibaut; Emberger, Michael; Felder, Thomas K; Feichtinger, René G; Koelblinger, Peter; Dallmann, Guido; Sonveaux, Pierre; Lang, Roland; Kofler, Barbara.
Affiliation
  • Weber DD; Research Program for Receptor Biochemistry and Tumor Metabolism, Department of Pediatrics, University Hospital of the Paracelsus Medical University, 5020, Salzburg, Austria.
  • Aminzadeh-Gohari S; Research Program for Receptor Biochemistry and Tumor Metabolism, Department of Pediatrics, University Hospital of the Paracelsus Medical University, 5020, Salzburg, Austria.
  • Thapa M; Biocrates Life Sciences AG, 6020, Innsbruck, Austria.
  • Redtenbacher AS; Research Program for Receptor Biochemistry and Tumor Metabolism, Department of Pediatrics, University Hospital of the Paracelsus Medical University, 5020, Salzburg, Austria.
  • Catalano L; Research Program for Receptor Biochemistry and Tumor Metabolism, Department of Pediatrics, University Hospital of the Paracelsus Medical University, 5020, Salzburg, Austria.
  • Capelôa T; Institut de Recherche Expérimentale et Clinique (IREC), Université catholique de Louvain (UCLouvain), 1200, Brussels, Belgium.
  • Vazeille T; Institut de Recherche Expérimentale et Clinique (IREC), Université catholique de Louvain (UCLouvain), 1200, Brussels, Belgium.
  • Emberger M; Patholab Salzburg, 5020, Salzburg, Austria.
  • Felder TK; Department of Laboratory Medicine, University Hospital of the Paracelsus Medical University, 5020, Salzburg, Austria.
  • Feichtinger RG; Research Program for Receptor Biochemistry and Tumor Metabolism, Department of Pediatrics, University Hospital of the Paracelsus Medical University, 5020, Salzburg, Austria.
  • Koelblinger P; Department of Dermatology and Allergology, University Hospital of the Paracelsus Medical University, 5020, Salzburg, Austria.
  • Dallmann G; Biocrates Life Sciences AG, 6020, Innsbruck, Austria.
  • Sonveaux P; Institut de Recherche Expérimentale et Clinique (IREC), Université catholique de Louvain (UCLouvain), 1200, Brussels, Belgium.
  • Lang R; Department of Dermatology and Allergology, University Hospital of the Paracelsus Medical University, 5020, Salzburg, Austria. r.lang@salk.at.
  • Kofler B; Research Program for Receptor Biochemistry and Tumor Metabolism, Department of Pediatrics, University Hospital of the Paracelsus Medical University, 5020, Salzburg, Austria. b.kofler@salk.at.
Cancer Metab ; 10(1): 12, 2022 Jul 18.
Article in En | MEDLINE | ID: mdl-35851093
BACKGROUND: Growing evidence supports the use of low-carbohydrate/high-fat ketogenic diets as an adjunctive cancer therapy. However, it is unclear which genetic, metabolic, or immunological factors contribute to the beneficial effect of ketogenic diets. Therefore, we investigated the effect of ketogenic diets on the progression and metabolism of genetically and metabolically heterogeneous melanoma xenografts, as well as on the development of melanoma metastases in mice with a functional immune system. METHODS: Mice bearing BRAF mutant, NRAS mutant, and wild-type melanoma xenografts as well as mice bearing highly metastatic melanoma allografts were fed with a control diet or ketogenic diets, differing in their triglyceride composition, to evaluate the effect of ketogenic diets on tumor growth and metastasis. We performed an in-depth targeted metabolomics analysis in plasma and xenografts to elucidate potential antitumor mechanisms in vivo. RESULTS: We show that ketogenic diets effectively reduced tumor growth in immunocompromised mice bearing genetically and metabolically heterogeneous human melanoma xenografts. Furthermore, the ketogenic diets exerted a metastasis-reducing effect in the immunocompetent syngeneic melanoma mouse model. Targeted analysis of plasma and tumor metabolomes revealed that ketogenic diets induced distinct changes in amino acid metabolism. Interestingly, ketogenic diets reduced the levels of alpha-amino adipic acid, a biomarker of cancer, in circulation to levels observed in tumor-free mice. Additionally, alpha-amino adipic acid was reduced in xenografts by ketogenic diets. Moreover, the ketogenic diets increased sphingomyelin levels in plasma and the hydroxylation of sphingomyelins and acylcarnitines in tumors. CONCLUSIONS: Ketogenic diets induced antitumor effects toward melanoma regardless of the tumors´ genetic background, its metabolic signature, and the host immune status. Moreover, ketogenic diets simultaneously affected multiple metabolic pathways to create an unfavorable environment for melanoma cell proliferation, supporting their potential as a complementary nutritional approach to melanoma therapy.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Type of study: Prognostic_studies Language: En Journal: Cancer Metab Year: 2022 Document type: Article Affiliation country: Austria Country of publication: Reino Unido

Full text: 1 Collection: 01-internacional Database: MEDLINE Type of study: Prognostic_studies Language: En Journal: Cancer Metab Year: 2022 Document type: Article Affiliation country: Austria Country of publication: Reino Unido