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Volume 22
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10.3390/ijms22126640
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Article

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

by
Magdalena Cal
1,*,
Irwin Matyjaszczyk
1,
Karolina Filik
2,
Rafał Ogórek
1,
Young Ko
3 and
Stanisław Ułaszewski
1
1
Department of Mycology and Genetics, University of Wroclaw, 51-148 Wroclaw, Poland
2
Laboratory of Medical Microbiology, Department of Immunology of Infectious Diseases, Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, 53-114 Wroclaw, Poland
3
KoDiscovery, LLC, Baltimore, MD 21202, USA
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2021, 22(12), 6640; https://doi.org/10.3390/ijms22126640
Submission received: 2 June 2021 / Revised: 16 June 2021 / Accepted: 18 June 2021 / Published: 21 June 2021
(This article belongs to the Special Issue Advances in Molecular Activity of Potential Drugs)
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Abstract

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.
Keywords: 3-bromopyruvate; mitochondria; superoxide generation; oxidative stress; mtDNA damage; yeast 3-bromopyruvate; mitochondria; superoxide generation; oxidative stress; mtDNA damage; yeast

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MDPI and ACS Style

Cal, M.; Matyjaszczyk, I.; Filik, K.; Ogórek, R.; Ko, Y.; Ułaszewski, S. Mitochondrial Function Are Disturbed in the Presence of the Anticancer Drug, 3-Bromopyruvate. Int. J. Mol. Sci. 2021, 22, 6640. https://doi.org/10.3390/ijms22126640

AMA Style

Cal M, Matyjaszczyk I, Filik K, Ogórek R, Ko Y, Ułaszewski S. Mitochondrial Function Are Disturbed in the Presence of the Anticancer Drug, 3-Bromopyruvate. International Journal of Molecular Sciences. 2021; 22(12):6640. https://doi.org/10.3390/ijms22126640

Chicago/Turabian Style

Cal, Magdalena, Irwin Matyjaszczyk, Karolina Filik, Rafał Ogórek, Young Ko, and Stanisław Ułaszewski. 2021. "Mitochondrial Function Are Disturbed in the Presence of the Anticancer Drug, 3-Bromopyruvate" International Journal of Molecular Sciences 22, no. 12: 6640. https://doi.org/10.3390/ijms22126640

APA Style

Cal, M., Matyjaszczyk, I., Filik, K., Ogórek, R., Ko, Y., & Ułaszewski, S. (2021). Mitochondrial Function Are Disturbed in the Presence of the Anticancer Drug, 3-Bromopyruvate. International Journal of Molecular Sciences, 22(12), 6640. https://doi.org/10.3390/ijms22126640

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