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Effect of 3-bromopyruvate acid on the redox equilibrium in non-invasive MCF-7 and invasive MDA-MB-231 breast cancer cells

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Abstract

Novel approaches to cancer chemotherapy employ metabolic differences between normal and tumor cells, including the high dependence of cancer cells on glycolysis (“Warburg effect”). 3-Bromopyruvate (3-BP), inhibitor of glycolysis, belongs to anticancer drugs basing on this principle. 3-BP was tested for its capacity to kill human non-invasive MCF-7 and invasive MDA-MB-231 breast cancer cells. We found that 3-BP was more toxic for MDA-MB-231 cells than for MCF-7 cells. In both cell lines, a statistically significant decrease of ATP and glutathione was observed in a time- and 3-BP concentration-dependent manner. Transient increases in the level of reactive oxygen species and reactive oxygen species was observed, more pronounced in MCF-7 cells, followed by a decreasing tendency. Activities of glutathione peroxidase, glutathione reductase (GR) and glutathione S-transferase (GST) decreased in 3-BP treated MDA-MB-231 cells. For MCF-7 cells decreases of GR and GST activities were noted only at the highest concentration of 3-BP.These results point to induction of oxidative stress by 3-BP via depletion of antioxidants and inactivation of antioxidant enzymes, more pronounced in MDA-MB-231 cells, more sensitive to 3-BP.

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Abbreviations

3-BP:

3-bromopyruvate

CDNB:

1-chloro-2,4-dinitrobenzene

DMSO:

dimethylsulfoxide

GR:

glutathione reductase

GSH:

glutathione (reduced)

GST:

glutathione S-transferase

MTT:

3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide

RNS:

reactive nitrogen species

ROS :

reactive oxygen species

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Acknowledgments

This work was supported by Grant 2012/07/B/NZ7/03618 from the National Science Centre in Poland. We are indebted to Miss Sabina Galiniak, M. Sc., for her help in statistical evaluation of results.

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Authors and Affiliations

  1. Department of Molecular Biophysics, Faculty of Biology and Environmental Protection, University of Lodz, Banacha 12/16, 90-237, Lodz, Poland

    Ewa Kwiatkowska, Martyna Wojtala, Agnieszka Gajewska & Mirosław Soszyński

  2. Department of Biochemistry and Cell Biology, Faculty of Biology and Agriculture, University of Rzeszów, Zelwerowicza 4, 35-601, Rzeszów, Poland

    Grzegorz Bartosz & Izabela Sadowska-Bartosz

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  1. Ewa Kwiatkowska
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  2. Martyna Wojtala
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  5. Grzegorz Bartosz
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  6. Izabela Sadowska-Bartosz
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Correspondence to Izabela Sadowska-Bartosz.

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Kwiatkowska, E., Wojtala, M., Gajewska, A. et al. Effect of 3-bromopyruvate acid on the redox equilibrium in non-invasive MCF-7 and invasive MDA-MB-231 breast cancer cells. J Bioenerg Biomembr 48, 23–32 (2016). https://doi.org/10.1007/s10863-015-9637-5

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  • DOI: https://doi.org/10.1007/s10863-015-9637-5

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