Mitochondrial Function Are Disturbed in the Presence of the Anticancer Drug, 3-Bromopyruvate

3-bromopuryvate (3-BP) is a compound with unique antitumor activity. It has a selective action against tumor cells that exhibit the Warburg effect. It has been proven that the action of 3-BP is pleiotropic: it acts on proteins, glycolytic enzymes, reduces the amount of ATP, induces the formation of...

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Bibliographic Details
Published in:International journal of molecular sciences 2021-06, Vol.22 (12), p.6640
Main Authors: Cal, Magdalena, Matyjaszczyk, Irwin, Filik, Karolina, Ogórek, Rafał, Ko, Young, Ułaszewski, Stanisław
Format: Article
Language:English
Subjects:
Antitumor activity
Apoptosis
Cancer
Cellular manufacture
Colorimetry
Dehydrogenases
DNA damage
Electron transport
Enzymes
Free radicals
Glycolysis
Metabolism
Mitochondria
Mitochondrial DNA
Organelles
Oxidative stress
Phosphorylation
Reactive oxygen species
Superoxide dismutase
Tumor cells
Yeast
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Summary:3-bromopuryvate (3-BP) is a compound with unique antitumor activity. It has a selective action against tumor cells that exhibit the Warburg effect. It has been proven that the action of 3-BP is pleiotropic: it acts on proteins, glycolytic enzymes, reduces the amount of ATP, induces the formation of ROS (reactive oxygen species), and induces nuclear DNA damage. Mitochondria are important organelles for the proper functioning of the cell. The production of cellular energy (ATP), the proper functioning of the respiratory chain, or participation in the production of amino acids are one of the many functions of mitochondria. Here, for the first time, we show on the yeast model that 3-BP acts in the eukaryotic cell also by influence on mitochondria and that agents inhibiting mitochondrial function can potentially be used in cancer therapy with 3-BP. We show that cells with functional mitochondria are more resistant to 3-BP than rho0 cells. Using an MTT assay (a colorimetric assay for assessing cell metabolic activity), we demonstrated that 3-BP decreased mitochondrial activity in yeast in a dose-dependent manner. 3-BP induces mitochondrial-dependent ROS generation which results in ∆sod2, ∆por1, or ∆gpx1 mutant sensitivity to 3-BP. Probably due to ROS mtDNA lesions rise during 3-BP treatment. Our findings may have a significant impact on the therapy with 3-BP.
ISSN:1422-0067
1661-6596
1422-0067
DOI:10.3390/ijms22126640