Metabolic therapies inhibit tumor growth in vivo and in silico

Scientific Reports
Jorgelindo Da Veiga MoreiraSabine Peres

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 20th 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 met...Continue Reading

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Citations

Aug 8, 2019·Microcirculation : the Official Journal of the Microcirculatory Society, Inc·Mehran Akbarpour GhazaniMadjid Soltani
Jan 11, 2020·Frontiers in Cell and Developmental Biology·Tatiana V DenisenkoBoris Zhivotovsky
Oct 13, 2020·Frontiers in Oncology·Jorgelindo da Veiga MoreiraMario Jolicoeur
Jul 22, 2020·Cancer Discovery·Michele CarboneGiovanni Gaudino
Aug 20, 2021·Scientific Reports·Menka KhoobchandaniKattesh V Katti

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Methods Mentioned

BETA
Human Genome Sequencing
xenograft

Software Mentioned

fmincon
MatWorks®
CellNetAnalyzer

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