Summary of Study ST001903

This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, where it has been assigned Project ID PR001198. The data can be accessed directly via it's Project DOI: http://dx.doi.org/10.21228/M8VD7F This work is supported by NIH grant, U2C- DK119886.

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This study contains a large results data set and is not available in the mwTab file. It is only available for download via FTP as data file(s) here.

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Study IDST001903
Study TitleEffect of ketogenic diet on the plasma and tumor metabolome of melanoma-bearing mice
Study TypeMetabolomics analysis
Study SummaryGrowing 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.
Institute
University Hospital of the Paracelsus Medical University Salzburg
Last NameWeber
First NameDaniela
AddressMüllner Hauptstraße 48, 5020 Salzburg, Austria
Emaild.weber@salk.at
Phone0043 57255 26274
Submit Date2021-08-10
Raw Data AvailableYes
Raw Data File Type(s)mzML
Analysis Type DetailLC-MS/MS(Dir. Inf.)
Release Date2022-07-11
Release Version1
Daniela Weber Daniela Weber
http://dx.doi.org/10.21228/M8VD7F
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

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Sample Preparation:

Sampleprep ID:SP002430
Sampleprep Summary:To capture a broad spectrum of metabolites, we used the MxP® Quant 500 kit combined with the in-house acylcarnitine (AC) assay (biocrates life sciences ag). Samples were prepared the same way for both assays. Therefore, 50-80 mg of tumor tissues were transferred to 0.5 ml Precellys® vials followed by the addition of 85:15 ethanol:0.01 M phosphate as a lysis buffer with a volume [µl] of 3 times the tissue weight [mg]. Tissue homogenization was carried out at 4 °C and 5800 rpm using a Precellys® 24 homogenizer coupled to a Cryolys® cooling unit. The homogenates were centrifuged at 10,000 g for 2 min at 2-4 °C. Supernatants were collected and stored at -80 °C until analysis. Plasma samples as well as tissue homogenate supernatant were thawed on ice, then vortexed before use.
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