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MetaboLights MTBLS1066 - GNPS Untargeted Metabolomics Reveals Molecular Effects of Ketogenic Diet on Healthy and Tumor Xenograft Mouse Models.

ABSTRACT: The application of ketogenic diet (KD) (high fat/low carbohydrate/adequate protein) as an auxiliary cancer therapy is a field of growing attention. KD provides sufficient energy supply for healthy cells, while possibly impairing energy production in highly glycolytic tumor cells. Moreover, KD regulates insulin and tumor related growth factors (like insulin growth factor-1, IGF-1). In order to provide molecular evidence for the proposed additional inhibition of tumor growth when combining chemotherapy with KD, we applied untargeted quantitative metabolome analysis on a spontaneous breast cancer xenograft mouse model, using MDA-MB-468 cells. Healthy mice and mice bearing breast cancer xenografts and receiving cyclophosphamide chemotherapy were compared after treatment with control diet and KD. Metabolomic profiling was performed on plasma samples, applying high-performance liquid chromatography coupled to tandem mass spectrometry. Statistical analysis revealed metabolic fingerprints comprising numerous significantly regulated features in the group of mice bearing breast cancer. This fingerprint disappeared after treatment with KD, resulting in recovery to the metabolic status observed in healthy mice receiving control diet. Moreover, amino acid metabolism as well as fatty acid transport were found to be affected by both the tumor and the applied KD. Our results provide clear evidence of a significant molecular effect of adjuvant KD in the context of tumor growth inhibition and suggest additional mechanisms of tumor suppression beyond the proposed constrain in energy supply of tumor cells.

INSTRUMENT(S): Q Exactive|1001911

ORGANISM(S): Mus Musculus|10090

SUBMITTER: David Licha

PROVIDER: MSV000085879 | GNPS | Sat Aug 01 12:51:00 BST 2020

REPOSITORIES: GNPS

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Project description:This ordinary differential equation model of the interactions between tumor and normal cells is based on the publication: S. A. Alharbi and A. S. Rambely, "Dynamic Simulation for Analyzing the Effects of the Intervention of Vitamins on Delaying the Growth of Tumor Cells," in IEEE Access, vol. 7, pp. 128816-128827, 2019 doi: 10.1109/ACCESS.2019.2940060. Comment: This TNM model is described by the system of equations presented in (2), in the publication manuscript. Abstract: The natural sources of the vitamins, which come from a balanced diet (as recommended by the World Cancer Research Fund and the American Institute for Cancer Research) contribute to protecting the body from advancing progressive of cancer stages. Thus, in this study, we analyze the effect of the intervention of vitamins on delaying the growth of cancer cells based on the dynamics of a normal cell cycle when the tumor cells appear in a tissue as a resulting for progressing abnormal cells due to the weak response of the immune system. We developed a mathematical model, called tumor-normal-vitamins model (TNVM), which is governed by a system of ordinary differential equations and refers to two main populations normal cells and tumor cells. This model considers the intervention of vitamins as a moderating factor within thirty days. The models are discussed analytically and numerically by utilizing the Runge-Kutta method to simulate them. The results of the analysis and simulation of free model illustrate that the model will be stable if the tumor cells succeed in eliminating normal cells in the tissue. Whereas, the analysis and simulation of the TNVM showed a case of coexistence between normal cells and tumor cells occur if an individual consumes a regular rate of vitamins that have been simulated to be 87% per day from a natural food source. Even though the response of the immune system is weak, the daily consumption of enough vitamins can play an essential role in delaying the development of an early stage of cancer. This study contributes to the increasing awareness regarding a healthy diet to reduce the risk of some deadly diseases, especially cancer.

Project description:This ordinary differential equation model of the interactions between tumor and normal cells, in the presence of a regular rate of vitamins, is based on the publication: S. A. Alharbi and A. S. Rambely, "Dynamic Simulation for Analyzing the Effects of the Intervention of Vitamins on Delaying the Growth of Tumor Cells," in IEEE Access, vol. 7, pp. 128816-128827, 2019 doi: 10.1109/ACCESS.2019.2940060. Comment: This TNVM model is described by the system of equations presented in (10), in the publication manuscript. Reproduction of Fig. 11 was achieved by swapping the values of gamma and beta2 stated in the manuscript, i.e. gamma = 0.9817 and beta2 = 0.2291. Abstract: The natural sources of the vitamins, which come from a balanced diet (as recommended by the World Cancer Research Fund and the American Institute for Cancer Research) contribute to protecting the body from advancing progressive of cancer stages. Thus, in this study, we analyze the effect of the intervention of vitamins on delaying the growth of cancer cells based on the dynamics of a normal cell cycle when the tumor cells appear in a tissue as a resulting for progressing abnormal cells due to the weak response of the immune system. We developed a mathematical model, called tumor-normal-vitamins model (TNVM), which is governed by a system of ordinary differential equations and refers to two main populations normal cells and tumor cells. This model considers the intervention of vitamins as a moderating factor within thirty days. The models are discussed analytically and numerically by utilizing the Runge-Kutta method to simulate them. The results of the analysis and simulation of free model illustrate that the model will be stable if the tumor cells succeed in eliminating normal cells in the tissue. Whereas, the analysis and simulation of the TNVM showed a case of coexistence between normal cells and tumor cells occur if an individual consumes a regular rate of vitamins that have been simulated to be 87% per day from a natural food source. Even though the response of the immune system is weak, the daily consumption of enough vitamins can play an essential role in delaying the development of an early stage of cancer. This study contributes to the increasing awareness regarding a healthy diet to reduce the risk of some deadly diseases, especially cancer.

Dataset Information

MetaboLights MTBLS1066 - GNPS Untargeted Metabolomics Reveals Molecular Effects of Ketogenic Diet on Healthy and Tumor Xenograft Mouse Models.

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