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Effect of ketogenic diet on the plasma and tumor metabolome of melanoma-bearing mice

ABSTRACT: Growing evidence supports the use of low-carbohydrate/high-fat ketogenic diets (KDs) together with standard therapies to improve cancer treatment outcomes. However, conflicting data exist regarding the efficacy of KDs in melanoma, the deadliest skin cancer. Here, we show that two different KD formulations effectively reduced tumor growth in immunocompromised mice bearing genetically and metabolically heterogeneous human melanoma xenografts. Furthermore, the KDs exerted a metastasis-reducing effect in an immunocompetent syngeneic melanoma mouse model. Ketone bodies did not directly influence melanoma cell proliferation; therefore, we performed an in-depth metabolomics analysis using the MxP® Quant 500 kit combined with a acylcarnitine assay (biocrates life sciences ag)to elucidate potential anti-tumor mechanisms in vivo. Targeted analysis of plasma and tumor metabolomes revealed distinct changes in amino acid metabolism induced by the KDs. Moreover, the KDs increased sphingomyelin synthesis and hydroxylation of certain lipids. Thus, KDs simultaneously affect multiple metabolic pathways to create an unfavorable environment for melanoma cell proliferation, supporting their potential as a complementary nutritional approach to melanoma therapy.

ORGANISM(S): Mouse Mus Musculus

TISSUE(S): Tumor Tissue, Blood

DISEASE(S): Cancer

SUBMITTER: Daniela Weber

PROVIDER: ST001903 | MetabolomicsWorkbench | Tue Aug 10 00:00:00 BST 2021

REPOSITORIES: MetabolomicsWorkbench

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