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Mechanisms of Redox Regulation of Chemoresistance in Tumor Cells by Phenolic Antioxidants

  • Cell Biophysics
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Abstract

Effects of water-soluble sulfur-containing phenolic antioxidants sodium 3-(3′-tert-butyl-4′- hydroxyphenyl)propyl thiosulfonate and potassium 3,5-dimethyl-4-hydroxybenzyl thioethanoate on chemoresistance in tumor cells have been studied. The studied phenolic antioxidants cause oppositely directed changes in the redox properties and chemoresistance in tumor cells. Potassium 3,5-dimethyl-4-hydroxybenzyl thioethanoate increases redox buffering capacity and doxorubicin resistance in tumor cells. Sodium 3-(3′- tert-butyl-4′-hydroxyphenyl)propyl thiosulfonate reduces the redox buffering capacity, which leads to a decrease in the chemoresistance of tumor cells. These observations suggest that one of the key mechanisms responsible for the formation of tumor cell resistance to antitumor compounds is the attenuation of apoptosis through increase of redox buffering capacity. The dependence of protein sensor redox state on oxidant concentrations and on redox buffering capacity in cells has been determined based on the proposed biophysical model of redox-dependent mechanism of apoptosis activation.

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Abbreviations

Keap1:

Kelch-like ECH-associated protein 1

Nrf2:

NF-E2-related factor 2

ARE:

antioxidant-response element

Klf9:

Kruppel-like factor 9

ROS:

reactive oxygen species

TS-13:

sodium 3-(3′-tert-butyl-4′-hydroxyphenyl)propylthiosulfonate

BEP-11-K:

potassium 3,5-dimethyl-4- hydroxybenzyl thioethanoate

DCF:

2′,7′-dichlorofluorescein

H2DCF:

2′,7′-dichlorodihydrofluorescein

NAC:

N-acetyl-Lcysteine

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Authors and Affiliations

  1. Belarusian State University, Minsk, 220030, Belarus

    G. G. Martinovich, I. V. Martinovich, A. V. Vcherashniaya, N. K. Zenkov & S. N. Cherenkevich

  2. Research Institute of Experimental and Clinical Medicine, Novosibirsk, 630117, Russia

    E. B. Menshchikova

  3. Novosibirsk State Pedagogical University, Novosibirsk, 630126, Russia

    N. V. Kandalintseva

Authors
  1. G. G. Martinovich
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  2. I. V. Martinovich
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  3. A. V. Vcherashniaya
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  4. N. K. Zenkov
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  5. E. B. Menshchikova
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  6. N. V. Kandalintseva
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  7. S. N. Cherenkevich
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Correspondence to G. G. Martinovich.

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Martinovich, G.G., Martinovich, I.V., Vcherashniaya, A.V. et al. Mechanisms of Redox Regulation of Chemoresistance in Tumor Cells by Phenolic Antioxidants. BIOPHYSICS 62, 942–949 (2017). https://doi.org/10.1134/S000635091706015X

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  • DOI: https://doi.org/10.1134/S000635091706015X

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