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Metabolic therapies inhibit tumor growth in vivo and in silico

Jorgelindo da Veiga Moreira, Minoo Hamraz, Mohammad Abolhassani, Laurent Schwartz, Mario Jolicoeur and Sabine Peres

Article (2019)

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Abstract

In the recent years, cancer research succeeded with sensitive detection methods, targeted drug delivery systems, and the identification of a large set of genes differently expressed. However, although most therapies are still based on antimitotic agents, which are causing wide secondary effects, there is an increasing interest for metabolic therapies that can minimize side effects. In the early 20(th) century, Otto Warburg revealed that cancer cells rely on the cytoplasmic fermentation of glucose to lactic acid for energy synthesis (called "Warburg effect"). Our investigations aim to reverse this effect in reprogramming cancer cells' metabolism. In this work, we present a metabolic therapy specifically targeting the activity of specific enzymes of central carbon metabolism, combining the METABLOC bi-therapeutic drugs combination (Alpha Lipoic Acid and Hydroxycitrate) to Metformin and Diclofenac, for treating tumors implanted in mice. Furthermore, a dynamic metabolic model describing central carbon metabolism as well as fluxes targeted by the drugs allowed to simulate tumors progression in both treated and non-treated mice, in addition to draw hypotheses on the effects of the drugs on tumor cells metabolism. Our model predicts metabolic therapies-induced reversed Warburg effect on tumor cells.

Subjects: 1800 Chemical engineering > 1800 Chemical engineering
1800 Chemical engineering > 1802 Biochemical engineering
Department: Department of Chemical Engineering
Research Center: Other
PolyPublie URL: https://publications.polymtl.ca/4836/
Journal Title: Scientific Reports (vol. 9, no. 1)
Publisher: Springer Nature
DOI: 10.1038/s41598-019-39109-1
Official URL: https://doi.org/10.1038/s41598-019-39109-1
Date Deposited: 20 Jul 2021 13:00
Last Modified: 23 May 2023 12:52
Cite in APA 7: da Veiga Moreira, J., Hamraz, M., Abolhassani, M., Schwartz, L., Jolicoeur, M., & Peres, S. (2019). Metabolic therapies inhibit tumor growth in vivo and in silico. Scientific Reports, 9(1). https://doi.org/10.1038/s41598-019-39109-1

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