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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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Autores principales: Cal, Magdalena, Matyjaszczyk, Irwin, Filik, Karolina, Ogórek, Rafał, Ko, Young, Ułaszewski, Stanisław
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8235118/
https://www.ncbi.nlm.nih.gov/pubmed/34205737
http://dx.doi.org/10.3390/ijms22126640
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author Cal, Magdalena
Matyjaszczyk, Irwin
Filik, Karolina
Ogórek, Rafał
Ko, Young
Ułaszewski, Stanisław
author_facet Cal, Magdalena
Matyjaszczyk, Irwin
Filik, Karolina
Ogórek, Rafał
Ko, Young
Ułaszewski, Stanisław
author_sort Cal, Magdalena
collection PubMed
description 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 rho(0) 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.
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spelling pubmed-82351182021-06-27 Mitochondrial Function Are Disturbed in the Presence of the Anticancer Drug, 3-Bromopyruvate Cal, Magdalena Matyjaszczyk, Irwin Filik, Karolina Ogórek, Rafał Ko, Young Ułaszewski, Stanisław Int J Mol Sci Article 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 rho(0) 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. MDPI 2021-06-21 /pmc/articles/PMC8235118/ /pubmed/34205737 http://dx.doi.org/10.3390/ijms22126640 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Cal, Magdalena
Matyjaszczyk, Irwin
Filik, Karolina
Ogórek, Rafał
Ko, Young
Ułaszewski, Stanisław
Mitochondrial Function Are Disturbed in the Presence of the Anticancer Drug, 3-Bromopyruvate
title Mitochondrial Function Are Disturbed in the Presence of the Anticancer Drug, 3-Bromopyruvate
title_full Mitochondrial Function Are Disturbed in the Presence of the Anticancer Drug, 3-Bromopyruvate
title_fullStr Mitochondrial Function Are Disturbed in the Presence of the Anticancer Drug, 3-Bromopyruvate
title_full_unstemmed Mitochondrial Function Are Disturbed in the Presence of the Anticancer Drug, 3-Bromopyruvate
title_short Mitochondrial Function Are Disturbed in the Presence of the Anticancer Drug, 3-Bromopyruvate
title_sort mitochondrial function are disturbed in the presence of the anticancer drug, 3-bromopyruvate
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8235118/
https://www.ncbi.nlm.nih.gov/pubmed/34205737
http://dx.doi.org/10.3390/ijms22126640
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