Study of the effect of methylene blue on tumor cell metabolism in vitro

Abstract

It is well known that cancer cells have characteristic changes in their metabolism. Switching from oxidative phosphorylation to aerobic glycolysis provides cancer cells with macromolecules for biosynthesis and rapid proliferation. Active glycolysis, in turn, leads to excessive accumulation of the coenzyme NADH and lactate. This creates reductive stress and maintains biosynthesis. Recently, it has been proposed to consider the effect on tumor metabolism as a therapeutic approach [1]. One of the substances capable of interfering with the metabolism of tumor cells is methylene blue (MB).
In this work, we investigated the effect of MB on key metabolic pathways (glycolysis, Krebs cycle, OXPHOS) using fluorescence and absorption spectroscopy, confocal and FLIM microscopy on cell cultures in vitro. Metabolic disorders (glycolysis, oxidative/reductive stress) were induced in cell cultures. Then, changes in mitochondrial membrane potential and activity of respiratory complexes were assessed, both before and after exposure with MB. The relationship between the NAD+/NADH ratio and mitochondrial function with the metabolic state of cells was studied by the lifetime of the coenzymes NADH and FAD. The ability of MB to influence the metabolism of tumor cells and promote a shift in metabolism towards oxidative phosphorylation was demonstrated.
The study was supported by the Russian Science Foundation (Project No. 22-72-10117-P).
[1] Xu, X., Peng, Q., Jiang, X. et al. Metabolic reprogramming and epigenetic modifications in cancer: from the impacts and mechanisms to the treatment potential. Exp Mol Med 55, 1357–1370 (2023)

Speaker

Daria Pominova
Prokhorov General Physics Institute of the Russian Academy of Sciences
Russia

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